Research Article Naja naja karachiensis …downloads.hindawi.com/journals/bmri/2014/970540.pdfNaja naja karachiensis Envenomation: Biochemical Parameters for Cardiac, Liver, and Renal

Research ArticleNaja naja karachiensis Envenomation BiochemicalParameters for Cardiac Liver and Renal Damage alongwith Their Neutralization by Medicinal Plants

Muhammad Hassham Hassan Bin Asad1 Ghulam Murtaza1

Muhammad Ubaid1 Durr-e-Sabih2 Ashif Sajjad3 Rubada Mehmood2

Qaisar Mahmood4 Muhammad Muzzmil Ansari5 Sabiha Karim6

Zahid Mehmood3 and Izhar Hussain1

1 Department of Pharmacy COMSATS Institute of Information Technology Abbottabad 22060 Pakistan2Multan Institute of Nuclear Medicine and Radiotherapy (MINAR) 377 Nishtar Hospital Multan 60000 Pakistan3 Institute of Biochemistry University of Balochistan Quetta 87300 Pakistan4Department of Environmental Sciences COMSATS Institute of Information Technology Abbottabad 22060 Pakistan5 Roba-al-Safwa Pharmacy Alsafwa Hospital 67 Makkah Saudi Arabia6University College of Pharmacy University of the Punjab Lahore 54000 Pakistan

Correspondence should be addressed to Ghulam Murtaza gmdogar356gmailcom and Izhar Hussain izharhussainciitnetpk

Received 17 January 2014 Accepted 27 March 2014 Published 27 April 2014

Academic Editor Andrei Surguchov

Copyright copy 2014 Muhammad Hassham Hassan Bin Asad et al This is an open access article distributed under the CreativeCommons Attribution License which permits unrestricted use distribution and reproduction in any medium provided theoriginal work is properly cited

Naja naja karachiensis envenomation was found to hit more drastically heart liver and kidneys 400 120583gkg of venom-raisedmoderate serum levels of ALT (72 plusmn 470UL 01 gt 119875 gt 005) AST (157 plusmn 2424UL 01 gt 119875 gt 005) urea (42 plusmn 308mgdL005 gt 119875 gt 002) creatinine (174 plusmn 003mgdL 001 gt 119875 gt 0001) CK-MB (21 plusmn 15UL 005 gt 119875 gt 002) and LDH(2064 plusmn 1598UL 119875 lt 0001) were injected in experimental rabbits However lethality was enhanced with 800120583gkg of venom interms of significant release of ALT (86plusmn50UL 005 gt 119875 gt 002) AST (251plusmn182UL 001 gt 119875 gt 0001) urea (576plusmn384mgdL002 gt 119875 gt 001) creatinine (21 plusmn 010mgdL 002 gt 119875 gt 001) CK-MB (77 plusmn 1122UL 005 gt 119875 gt 002) and LDH(2562 plusmn 2514UL 119875 ≪ 0001) Among twenty-eight tested medicinal plant extracts only Stenolobium stans (L) Seem was foundthe best antivenom (119875 gt 05) compared to the efficacy of standard antidote (ALT = 525 plusmn 351UL AST = 695 plusmn 1855UL urea= 315 plusmn 050mgdL creatinine = 108 plusmn 002mgdL CK-MB = 09 plusmn 085UL and LDH = 763 plusmn 601UL) Other plant extractswere proved less beneficial and partly neutralized the toxicities posed by cobra venom However it is essential in future to isolateand characterize bioactive compound(s) from Stenolobium stans (L) Seem extract to overcome the complications of snake bite

1 Introduction

One of the animals which represent Pakistan and Indiathroughout the world is cobra in particular it is rearing out ofa wicker basket and dancing to the sound of turban-wearingsnake charmer music In fact they are deadly venomousamong all species of the snakes due to high rate of mortalitywhich strongly reasoned for their notoriety [1] At the endof the nineteenth century all cobra populations have beenmerged into single species naja (formerly known as naia)

however subsequently ten subspecies of Naja naja wereidentified [1] Later on Deraniyagala classified Naja naja(India) into several subspecies and considered Naja najakarachiensis one of them widely distributed in SouthernPunjab province of Pakistan [2] They are extremely toxicdue to their severe side effects in the victims Major signsand symptoms of cobra envenomation are edema necrosispain respiratory paralysis vomiting headache hypotensioncardiac arrest coagulopathies (elevated PT aPTT and TT)bleeding wounds hematuria mucus discharge proteinuria

Hindawi Publishing CorporationBioMed Research InternationalVolume 2014 Article ID 970540 13 pageshttpdxdoiorg1011552014970540

2 BioMed Research International

and increased creatinine and urea levels along with alteredconsciousness [3 4]

Indeed snake venom is a complex mixture of varioussizes of polypeptides [5 6] (lt15 kDa 5 to 10 kDa and10 to 150 kDa) carbohydrates lipids metal ions organicmolecules purines and amines [7 8] Snake bite enveno-mation has been attributed to pose drastic changes in thephysiology of the victims that could be accessed clinicallyby measuring various biochemical parameters Among toxiccomponents phospholipases A

2(cell destroying enzymes

cause edema lipolytic or myolytic) [9 10] phosphodi-esterases (nucleic acid degrading enzyme causes hypoten-sionshock) [11 12] 51015840 nucleotidases (digest the sugar moitiescausing the delay in coagulation) [13] alkaline phosphatases(hydrolyze phosphate esters nonspecifically cause multipletoxicities via adenosine generation) [14] hyaluronidases(spreading factor causes digestion necrosis and leakage ofblood vessels) [15] L-amino oxidases (deamination leads tocell damageapoptosis) [16] and proteases (hydrolyze variousproteins) [17] are included

Laboratory animals particularly rabbits have beenselected previously to monitor various biochemical changesrelated to liver heart and renal toxicities [18 19] Aspartateaminotransferase (GOTAST) and alanine aminotransferase(GPTALT) are surrogate markers for liver toxicities whilecreatine kinase isoenzyme (CK-MB) is used exclusively toaccess cardiac tissue damage [20 21] Elevated creatinine andurea levels are indicators of 75 renal damage [20] whereashigh level of lactate dehydrogenase (LDH) implies generaltoxicity related to the liver heart kidneys and skeletonmuscles [22]

Diverse immunological properties of different cobrashave fascinated protein chemists and other researchers tocarry out efforts for the development of new antidotes Dueto this reason for the first time venom from Naja najakarachiensis is selected to evaluate its toxicity in vivo andto search out effective as well as cheap treatment fromfolk herbal remedies Pakistan is a hub of medicinal plantswhere mostly rural communities rely on natural herbs totreat their problems of snake bite [6 23] It is thereforenecessary to evaluate scientifically their folklore claims asanti-snake venom in traditional system of medicine Dueto this reason various medicinal plants (Albizia lebbeck (L)Benth Allium cepa L Allium sativum L Althaea officinalisL Bauhinia variegata L Brassica nigra (L) W D J KochCalotropis procera (Aiton)WTAitonCedrus deodara (Roxbex D Don) G Don Citrullus colocynthis (L) Schrad Citruslimon (L) Burm f Cuminum cyminum L Enicostemahyssopifolium (Willd) I Verd Fagonia cretica L Leucascapitata DesfMatthiola incana (L) W T AitonMomordicacharantiaLNerium indicumMillOcimum sanctumL Pinusroxburghii Sarg Pistacia integerrima J L Stewart Psoraleacorylifolia L Rhazya stricta Decne Rubia cordifolia LSapindus mukorossi Gaertn Solanum xanthocarpum Schardand Wendle Stenolobium stans (L) Seem Terminalia arjuna(Roxb exDC)Wight andArnTrichodesma indicum (L) Smand Zingiber officinale Roscoe) were collected to test theirpotentials against toxicities induced byNaja naja karachiensisenvenomation (Table 1)

2 Material and Methods

21 Collection and Milking of Snake Venom Black Pakistanicobra snakes (Naja naja karachiensis) were collected fromCholistan desert located in southern Punjab province ofPakistan After collection they were properly identified by azoologist Venom from Naja naja karachiensis was collectedby pressing their glands below their eyes in low light environ-ment After collection it was lyophilized and stored in lightresistant container at 2∘C to 8∘C For further experimentsvenom was used in terms of its dry weight [6]

22 Collection and Preparation of Plant Extracts Medicinalplants were collected from different areas in Pakistan Aftercollection they were duly identified by expert botanist(Professor Dr Altaf Ahmad Dasti) and voucher specimenswere deposited in the herbarium of the Institute of Pure andApplied Biology Bahauddin Zakariya University MultanPakistan Complete description about evaluated medicinalplants is summarized in Table 1 One kilogram choppedplant material was soaked in 5 L of methanol as solvent inextraction bottlesThe homogenates were kept for a period ofa month at optimum temperature After filtration filtrate wasevaporated by using water bath and extracts were weighedand stored for further experimentation [24]

23 Experimental Animals Seventy-one healthy growingmale rabbits (1 plusmn 05 kg) were selected for this study aftergetting permission from local ethical committee Animalswere acclimatized for a week in the laboratory bymaintainingtheir standards for chow water and light Subsequently theywere divided into various groups in different cages suchthat experimental rabbits in group I were used for baselinemeasurements of various biochemical parameters Animalsbelonging to groups II and III were evaluated for differentdoses of cobra venom while group IV was served as controlGroup V was redivided into twenty-nine groups such thateach subgroup (V1ndashV29) was assigned to a single medicinalplant extract [25]

24 In Vivo Antivenom Activity of Medicinal Plant ExtractsVenom from Naja naja karachiensis (400 120583gkg and800 120583gkg) was injected subcutaneously to evaluate itstoxicity to the heart liver and kidneys Before injectionof venom experimental animals were anaesthetizedby administration of ketamine (50mgkg) To determineantivenomactivity of various plantsrsquo extract they (100mgkg)were incubated (at 37∘C for 30 minutes) with fixed amountof venom (800120583gkg) before injection while saline was usedas control [26ndash28]

25 Biochemical Assays For serum analysis of various bio-chemical parameters blood was collected from marginal earartery by the use of hypodermic syringe needle after 3 hoursof envenomation [25] Separated serumwas tested for alanineaminotransferase (GPTALT) aspartate aminotransferase(GOTAST) urea creatinine creatine kinase isoenzyme MB(CK-MB) and lactate dehydrogenase (LDH) by the use of

BioMed Research International 3

Table1Detaileddescrip

tionfore

valuated

medicinalplantshaving

folklore

evidencesa

santivenom

Srnum

ber

Botanicaln

ameo

fmedicinalplants

Family

Partused

Phytochemicalsreported

Reference

1Albizialeb

beck

(L)Be

nth

Fabaceae

Seed

Carboh

ydratesproteinsalkaloidsflavanoidstanninsechinocystic

acidand

different

aminoacids

[6]

2Alliu

mcepa

LAmaryllid

aceae

Bulb

11gcarboh

ydrates12

gproteins06gfib

ersandH

2Ocontent(868g)10

0gof

material

[6]

3Alliu

msativ

umL

Amaryllid

aceae

Bulb

Quercetinscordinines

AandBallicinthiosulfin

ates2

mercapto-L-cyste

ines

anthocyaninsalliinasepo

lysaccharid

essativin

Iand

sativ

inIIand

glycosides

ofkaem

pferol

[6]

4Althaeaoffi

cinalisL

Malvaceae

Root

37sta

rch11mucilagefattyoilpectinflavon

oidspheno

licacidsasparagines

phytosterolsucroseandbu

tyric

acid

[6]

5Ba

uhiniavarie

gata

LFabaceae

Root

Tann

insfatty

oillupeolkaempferol-3-glucosid

egums120573-sito

sterol57-dehydroxy

and57-dimetho

xy-flavanon

e-4-0-a-L-rham

nopyrano

syl-120573

-Dglucop

yranosides

[6]

6Brassicanigra(L)WD

JK

och

Brassic

aceae

Seed

Essentialoilsin

igrin

andglucoside

[6]

7Ca

lotro

pisp

rocera

(Aito

n)WTA

iton

Apocyn

aceae

Exud

ates

andflo

wer

Resin

stann

inscalotro

pin

steroluscharincalotropagenin

calotoxin

andcalactin

[6]

8Ce

drus

deodara(Roxbex

DD

on)G

Don

Pinaceae

Bark

Taxifolin

dew

ardioldew

arenegumascorbica

cidhimadarolcantdarol

cholesterin

allo

himachalolcedrinosidehimachaloldewarolcedrin

dihydrod

ehydrodiconiferylalcoh

olessentia

loiliso

centdaroland

dihydrom

yricetin

[6]

9Citru

slim

on(L)Bu

rmf

Rutaceae

Fruit

4-120573-glucopyrano

sided-x-pinene

camph

ened-lim

onenelin

aloo

lichangin


sideno

milinica

cidandessentialoil

[6]

10Citru

lluscolocynthis(L)Schrad

Cucurbita

ceae

Fruit

Manyalkaloidsglycosidestanninscitrulluincitrulluicaciddihydric

alcoho

lph

ydroxybenzylcitrulluenehentria

contaneelaterincitrullolmethyletherbitter

oilcitbittoland

sapo

nins

[6]

11Cu

minum

cyminum

LAp

iaceae

Seed

Essentialoilandcumin

oilcon

tain

sminaldehyde13-p-m

enthadien-7-aland

14-p-m

enthadien-7-al

[6]

12En

icoste

mahysso

pifoliu

m(W

illd)IV

erd

Gentia

naceae

Who

leplant

Sapo

narin

isovetexin

sylysw

ertin

betulinswertia

marinapigenin

genk

wanin

erythrocentaurinesw

ertio

sideiso

swertisinenicoflavineand

swertisin

[6]

13Fagoniacretica

LZy

goph

yllaceae

Leaves

Ursolicacidpinito

lnahagenin

sapo

ninglycosidessapon

in-Iandsapo

nin-II

docosyld

ocosanoatefro

mn-hexane

extractanddifferent

proteins

from

aqueou

sextract

[6]

14Leucas

capitataDesf

Lamiaceae

Who

leplant

Alkaloidas

wellase

ssentia

loil

[6]

15Matthiolaincana

(L)WTA

iton

Brassic

aceae

Seeds

Oilric

hin

chloroph

yllsabNPK

and

Na120574-lino

lenica

cidandcaroteno

ids

Sulfo

raph

eneisa

nim

portantcom

ponent

[6]

16Mom

ordica

charantia

LCu

curbita

ceae

Fruit

Caroteno

idsmom

orcharasides

AandB

glucosidesstig

mastadien-3-beta-ol

squalenem

ycosessteroidalglucosidemom

ordicinesI

andIIstig

masterolvicine

cucurbitane

triterpenoidsm

omordicosid

escycloeucaleno

ltaraxerol

spinasterollo

phenoldiosgeninthiocyano

gen

24-m

ethylencycloarteno

land

phenylprop

anoids

[6]

17Ne

rium

indicum

Mill

Apocyn

aceae

Root

andleaves

Nerioderin

neriodo

rinkarabinand

odorin

[6]

18Ocim

umsanctum

LLamiaceae

Who

leplant

Essentialoils

arefou

ndric

hin

32

carvacrol713eugeno

l17

caryop

hyllene

204methyleugenoleugenolmethyletherlinaloo

landmethylchavicolcineole

[6]


Table1Con

tinued

Srnum

ber

Botanicaln

ameo

fmedicinalplants

Family

Partused


Reference

19Pinu

sroxburghiiSarg

Pinaceae

Oleoresin

Careen120572

-pinene120573-pinene120573-carene120573-lo

ngifo

lenelon

gifoleneand

long

icyclene

[6]

20Pista

ciaintegerrim

aJLStewart

Anacardiaceae

Galls

13essentialoilric

hin

camph

enecineoleA-

terpineolA-

pinenearomadendrene

caprylicacidand

d-lim

onenea

bund

antingalls

[6]

21Psoralea

corylifoliaL

Fabaceae

Seeds

Limon

enelin

aloo

lpsoraleneangelicinn

eobavachalconebakuchiol4-te

rpineol

corylid

inn

eobavaiso

flavonebavachinin

isobavachin120572

-elemenegeranylacetate

stigmasterolbaku

chioltraincon

taneisopsoralidinisopsoralenbakuchalcon

eiso

neob

avachalcon

epsoralenpsoralid

inraffi

nosecorylifo

linincorylifo

leanand

corylifolin

[6]

22Rh

azya

strictaDecne

Apocyn

aceae

Leaves

Enzymes

(NADPH

depend

ent)

glycosides

(rob

lnin3-7-rhamno

sidea

ndiso

rham

netin

-3-7-rhamno

side)alkaloid(sew

arine)and

triterpenes

(ursolicacid

Mgqu

inateand120573-sito

sterol)alon

gwith

flavono

idsrhazianosides

AandB

[6]

23Ru

biacordifolia

LRu

biaceae

Stem

Pseudo

purpurinxanthop

urpu

rinpurpu

rinm

unjistin

alizarinand

mun

jistin

are

foun

dwith

theirg

lycosid

es

[6]

24Sapind

usmukorossiGaertn

Sapind

aceae

Fruit120573-Sito

sterolsapind

osideA

sapindo

sideB

kaempferolquercetinsapon

inand

emarginatosid

e[6]

25Stenolob

ium

stans

(L)Seem

Bign

oniaceae

Root120573-C

arotene120573-sito

sterol120572-amarinezeaxanthinind

olem

etabolizingenzymes

phenolicacidsoleano

licacidtriterpeno

idsursolic

acidind

ole-oxygenaseand

luteinzeaxanthin

[6]

26Term

inaliaarjuna

(Roxbex

DC)W

ight

andArn

Com

bretaceae

Bark120573-Sito

sterolarjuno

licacidtom

entosic

acidellagica

cidessentialoilarjunetin

arjuninecalcium

saltsaluminium

andmagnesiu

msaltscoloringagents

redu

cing

sugarstannin(pyrocatecho

l)andalactone

[6]

27Trich

odesmaindicum

(L)Sm

Boraginaceae

Who

leplantSeedso

ilisric

hin

linoleicoleicste

aricpalmiticandlin

olenicacidsAp

arto

fit

hexacosaneethylhexacosano

ateand2124-hexacos-adieno

icacid

ethyleste

rsare

foun

d[6]

28Zingiberoffi

cinaleR

oscoe

Zing

iberaceae

Rhizom

eD-C

urcumenecineolpotassiu

moxalatecamph

enecitralbo

rneolsin

giberin

eshogaol120572-curcumene120572-bergamotene120573-gam

ma-bisabo

lenegingeroland

120573-phelland

rene

23


Table2Biochemicalparametersb

eforea

ndaft

ersnakev

enom

administratio

nin

different

experim

entalgroup

sofrabbits

Toxicitydeterm

ined

Markersof

snake

veno

mtoxicity

Group

Ibaseline

measurements

(meanplusmnSE

M)

Group

IIandIIIv

enom

injection

Group

IVnegativ

econ

trol

(meanplusmnSE

M)

Normalreference

values

repo

rted

References

04m

gkg

(meanplusmnSE

M)

08m

gkg

(meanplusmnSE

M)

Liver

GPT

ALT

(52plusmn346

)UL

(72plusmn470)U

L01gt119875gt005

(86plusmn50)

UL

005gt119875gt002

(52plusmn348)U

L(48ndash80)U

L[19

]

GOTAST

(65plusmn657)U

L(157plusmn2424)

UL

01gt119875gt005

(251plusmn182)U

L001gt119875gt0001

(67plusmn321)U

L(14

ndash113)U

L[19

]

Kidn

eys

Urea

(28plusmn17

3)mgdL

(42plusmn308)m

gdL

005gt119875gt002

(576plusmn384)m

gdL

002gt119875gt001

(28plusmn033)m

gdL

(10ndash

28)m

gdL

[26]

Creatin

ine

(10plusmn0313)

mgdL

(174plusmn003)m

gdL

001gt119875gt0001

(21plusmn010)m

gdL

002gt119875gt001

(1plusmn006)m

gdL

(05ndash25)m

gdL

[26]

Heart

CK-M

B(132plusmn20)

UL

(21plusmn

15)U

L005gt119875gt002

(77plusmn1122)

UL

005gt119875gt002

(13plusmn056)U

L(lt25)U

Llowast

[2021]

LDH

(714plusmn318)U

L(206

4plusmn1598)

UL

119875lt0001

(2562plusmn2514

)UL

119875≪0001

(720plusmn470)U

L(559ndash2077)

UL

[46]

lowastCK

-MBactiv

ityislessthan

2in

healthyrabbitshow

everitisu

sually10ndash30

oftotalC

Kactiv

ity


0

50

100

150

200

250

300Se

rum

leve

l of G

PTG

OT

(UL

)

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

LRh

azya

stric

ta D

ecne

Rubi

a co

rdifo

lia L

Sa

pind

us m

ukor

ossi

Gae

rtn

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C) W

ight

and

Arn

Trich

odes

ma

indi

cum

(L)

SmZi

ngib

er o

fficin

ale R

osco

eRe

fere

nce s

tand

ard

anti

dote

GPT levelGOT level

Various antidotes used (100mgkg)

Figure 1 Comparison of various medicinal plant extracts with reference standard antidote in neutralization of increased GPT and GOTserum level posed by Naja naja karachiensis venom in rabbits

kits (manufactured by Merck) according to the DGKC andIFCCmethod on the Selectra Junior (Vital Scientific BVTheNetherlands) [26]

26 Statistical Analysis All numerical values were expressedas mean (3 replicates) plusmn standard error of mean (SEM) Theywere calculated by the use of Microsoft Excel 2007 and Stu-dentrsquos t-test was applied to compare the efficacy of evaluatedsamples with standard antidote (reference standard)

3 Results

Venom from Naja naja karachiensis was proved to causesevere complications in dose-dependent manner Venom atthe dose of 400 120583gkg led to release of moderate serum levelsof ALT (72plusmn470UL 01 gt 119875 gt 005) AST (157plusmn2424UL01 gt 119875 gt 005) urea (42 plusmn 308mgdL 005 gt 119875 gt 002)creatinine (174 plusmn 003mgdL 001 gt 119875 gt 0001) CK-MB(21 plusmn 15UL 005 gt 119875 gt 002) and LDH (2064 plusmn 1598UL119875 lt 0001) and thus indicated toxicities to the heart liver andkidneys At 800 120583gkg of cobra venom severe tissue damagewas observed in terms of significant release of ALT (86 plusmn50UL 005 gt 119875 gt 002) AST (251 plusmn 182UL 001 gt 119875 gt0001) urea (576 plusmn 384mgdL 002 gt 119875 gt 001) creatinine

(21 plusmn 010mgdL 002 gt 119875 gt 001) CK-MB (77plusmn 1122UL005 gt 119875 gt 002) and LDH (2562 plusmn 2514UL 119875 ≪ 0001)Complete detail about various biochemical parameters forbaseline measurements different doses of cobra venom andsaline (as negative control) is summarized in Table 2

To neutralize in vivo 800 120583gkg of cobra venom twenty-eight medicinal plant extracts were evaluated It was noticedthat extract of Stenolobium stans (L) Seem was the bestantidote (119875 gt 05) compared to reference standard Alliumsativum L Althaea officinalis L Citrullus colocynthis (L)Schrad Leucas capitataDesf Pinus roxburghii Sarg Psoraleacorylifolia L Rubia cordifolia L and Sapindus mukorossiGaertn were found to be valuable plants to protect liverdamage (119875 gt 05) as standard antidote (ALT = 525 plusmn351UL and AST = 695 plusmn 1855UL) however requiredALT and AST levels were not observed with remainingplant extracts (05 gt 119875 gt 005) as shown in Table 3 andcomparison is shown in Figure 1 Extracts of Leucas capitataDesf and Althaea officinalis L were observed to be helpful(119875 gt 05) as reference standard (urea = 315 plusmn 050mgdLand creatinine = 108 plusmn 002mgdL) nevertheless remainingplants were found less valuable (05 gt 119875 gt 001) tominimize urea and creatinine levels to maintain kidney func-tions (Table 4 and Figure 2) When compared with standardantidote (CK-MB = 90 plusmn 085UL) eight medicinal plants


Table 3 Hepatoprotective activity of various medicinal plant extracts on ALT and AST levels to neutralize snake bite envenomation inexperimental rabbits

Sr number Group V(subgroup) Name of evaluated sample GPTALT GOTAST

UL(mean plusmn SEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment

1 (V1) Albizia lebbeck (L) Benth 62 plusmn 702 05 gt 119875 gt 01 99 plusmn 1855 05 gt 119875 gt 01

2 (V2) Allium cepa L 68 plusmn 1203 05 gt 119875 gt 01 1665 plusmn 050 05 gt 119875 gt 01

3 (V3) Allium sativum L 49 plusmn 501 119875 gt 05 825 plusmn 1855 119875 gt 05

4 (V4) Althaea officinalisL 70 plusmn 2005 119875 gt 05 745 plusmn 1454 119875 gt 05

5 (V5) Bauhinia variegata L 78 plusmn 404 05 gt 119875 gt 01 1495 plusmn 199 05 gt 119875 gt 01

6 (V6) Brassica nigra (L) W D J Koch 45 plusmn 000 05 gt 119875 gt 01 55 plusmn 100 119875 gt 05

7 (V7a) Calotropis procera (Aiton) W TAiton (exudates) 315 plusmn 05 05 gt 119875 gt 01 141 plusmn 101 05 gt 119875 gt 01

8 (V7b) Calotropis procera (Aiton) W TAiton (flowers) 625 plusmn 252 05 gt 119875 gt 01 194 plusmn 1212 05 gt 119875 gt 01

9 (V8) Cedrus deodara (Roxb ex DDon) G Don 633 plusmn 414 05 gt 119875 gt 01 72 plusmn 202 119875 gt 05

10 (V9) Citrus limon (L) Burm f 305 plusmn 1363 05 gt 119875 gt 01 49 plusmn 2424 119875 gt 05

11 (V10) Citrullus colocynthis (L) Schrad 475 plusmn 555 119875 gt 05 74 plusmn 909 119875 gt 05

12 (V11) Cuminum cyminum L 67 plusmn 1616 119875 gt 05 157 plusmn 1414 05 gt 119875 gt 01

13 (V12) Enicostemma hyssopifolium(Willd) I Verd 8525 plusmn 126 01 gt 119875 gt

0051685 plusmn 757 05 gt 119875 gt 01

14 (V13) Fagonia cretica L 80 plusmn 782 05 gt 119875 gt 01 170 plusmn 1313 05 gt 119875 gt 01

15 (V14) Leucas capitata Desf 455 plusmn 752 119875 gt 05 535 plusmn 050 119875 gt 05

16 (V15) Matthiola incana (L) W T Aiton 62 plusmn 808 05 gt 119875 gt 01 121 plusmn 505 05 gt 119875 gt 01

17 (V16) Momordica charantia L 625 plusmn 752 05 gt 119875 gt 01 247 plusmn 4613 05 gt 119875 gt 01

18 (V17) Nerium indicumMill 88 plusmn 1955 05 gt 119875 gt 01 235 plusmn 1805 01 gt 119875 gt

005

19 (V18) Ocimum sanctum L 615 plusmn 752 05 gt 119875 gt 01 158 plusmn 1002 05 gt 119875 gt 01

20 (V19) Pinus roxburghii Sarg 53 plusmn 902 119875 gt 05 57 plusmn 1303 119875 gt 05

21 (V20) Pistacia integerrima J L Stewart 415 plusmn 15 05 gt 119875 gt 01 545 plusmn 050 119875 gt 05

22 (V21) Psoralea corylifolia L 54 plusmn 100 119875 gt 05 665 plusmn 1153 119875 gt 05

23 (V22) Rhazya stricta Decne 66 plusmn 2424 119875 gt 05 1325 plusmn 1262 05 gt 119875 gt 01

24 (V23) Rubia cordifolia L 655 plusmn 1767 119875 gt 05 129 plusmn 6641 119875 gt 05

25 (V24) Sapindus mukorossi Gaertn 56 plusmn 601 119875 gt 05 785 plusmn 1354 119875 gt 05

26 (V25) Stenolobium stans (L) Seem 465 plusmn 656 119875 gt 05 705 plusmn 353 119875 gt 05

27 (V26) Terminalia arjuna (Roxb exDC) Wight and Arn 475 plusmn 151 05 gt 119875 gt 01 78 plusmn 606 119875 gt 05

28 (V27) Trichodesma indicum (L) Sm 52 plusmn 000 119875 gt 05 125 plusmn 401 05 gt 119875 gt 01

29 (V28) Zingiber officinale Roscoe 665 plusmn 3259 119875 gt 05 1175 plusmn 952 05 gt 119875 gt 01

30 (V29)Reference standard antidote(standard antiseraimmunoglobulinrsquos)

525 plusmn 351 Select tocompare 695 plusmn 1855 Select to

compare

(Allium cepa L Althaea officinalis L Bauhinia variegataL Cedrus deodara (Roxb ex D Don) G Don Fagoniacretica L Leucas capitataDesf Momordica charantia L andOcimum sanctum L) were found equally capable (119875 gt 05) ofnormalizing high values of CK-MB however rest of all wereproved less beneficial (05 gt 119875 gt 01) To combat highlyraised values of LDH Althaea officinalis L Leucas capitataDesf and Terminalia arjuna (Roxb ex DC) Wight and Arnwere proved useful to some extent (05 gt 119875 gt 01) although

remaining plant extracts could not be shortlisted (01 gt 119875 gt0001) as standard antisera (LDH = 763 plusmn 601UL) Overalldetail about LDH is discussed in Table 5 and comparison isshown in Figure 3

4 Discussion

Snake bite has been responsible for tens of thousands ofdeaths worldwide and numerous physical handicaps [29]


Table 4 Nephroprotective activity of different medicinal plant extracts on urea and creatinine levels to neutralize snake bite envenomationin experimental rabbits

Sr number Group V(subgroup) Name of evaluated sample Urea Creatinine

mgdL(mean plusmn SEM)

119875 valuecomment


119875 valuecomment



3 (V3) Allium sativum L 50 plusmn 401 05 gt 119875 gt 01 130 plusmn 006 05 gt 119875 gt 01






9 (V8) Cedrus deodara (Roxb ex DDon) G Don 44 plusmn 404 05 gt 119875 gt 01 144 plusmn 007 05 gt 119875 gt 01

10 (V9) Citrus limon (L) Burm f 395 plusmn 252 05 gt 119875 gt 01 140 plusmn 003 01 gt 119875 gt 005

11 (V10) Citrullus colocynthis (L) Schrad 495 plusmn 353 05 gt 119875 gt 01 152 plusmn 015 05 gt 119875 gt 01

12 (V11) Cuminum cyminum L 54 plusmn 101 005 gt 119875 gt 002 148 plusmn 001 005 gt 119875 gt 002

13 (V12) Enicostemma hyssopifolium(Willd) I Verd 395 plusmn 454 05 gt 119875 gt 01 135 plusmn 005 05 gt 119875 gt 01

14 (V13) Fagonia cretica L 43 plusmn 227 05 gt 119875 gt 01 123 plusmn 013 119875 lt 05




18 (V17) Nerium indicumMill 47 plusmn 000 119875 lt 005 124 plusmn 010 05 gt 119875 gt 01


20 (V19) Pinus roxburghii Sarg 45 plusmn 100 119875 gt 005 14 plusmn 005 05 gt 119875 gt 01

21 (V20) Pistacia integerrima J L Stewart 665 plusmn 050 002 gt 119875 gt 001 168 plusmn 010 05 gt 119875 gt 01

22 (V21) Psoralea corylifolia L 425 plusmn 250 05 gt 119875 gt 01 127 plusmn 015 05 gt 119875 gt 01

23 (V22) Rhazya stricta Decne 535 plusmn 353 05 gt 119875 gt 01 167 plusmn 0005 005 gt 119875 gt 002

24 (V23) Rubia cordifolia L 36 plusmn 101 05 gt 119875 gt 01 093 plusmn 048 119875 gt 05

25 (V24) Sapindus mukorossi Gaertn 44 plusmn 100 01 gt 119875 gt 005 143 plusmn 012 05 gt 119875 gt 01



28 (V27) Trichodesma indicum (L) Sm 37 plusmn 100 05 gt 119875 gt 01 046 plusmn 001 005 gt 119875 gt 002

29 (V28) Zingiber officinale Roscoe 47 plusmn 100 005 gt 119875 gt 002 130 plusmn 001 05 gt 119875 gt 01



compare

Generally snake venom is an intricate mixture of variousproteins (gt90) and most of them are enzymes particularly(40) phospholipases A

2[30] Among different complica-

tions hepatic injury is one of the deadly venomous effectsproduced by cobra bite [31 32] Naja naja karachiensisvenom caused significant increase in ALT and AST levels(dose dependently) that are surrogate markers for livertoxicity either by direct action or immunological (hyper-sensitivity) reaction The allergic reactions reactions are notdose dependent which clarify lethal effects to the cytoplasm

and mitochondrial membranes of the hepatic cells [25 33]Phospholipases enzymes abundant in Naja naja karachien-sis venom are responsible for breakdown of membranousphospholipids and therefore resulted in cellular injury alongwith inflammation [24] PLA

2is attributed to decrease in

Na+K+ ATPase activities and led to greater influx of sodiumions and water molecules into the cell Subsequently plasmamembrane lipid bilayer disorganized and eventually resultedin hepatic cells death [33 34] In addition PLA

2is also found

to cause anticoagulation in victims [6] All pharmacological


Table 5 Cardioprotective activity of medicinal plant extracts on LDH and CK-MB levels to neutralize snake bite envenomation inexperimental rabbits

Sr numberGroup V(subgroup) Name of evaluated sample LDH CK-MB

UL (mean plusmnSEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment


2 (V2) Allium cepa L 934 plusmn 1303 01 gt 119875 gt 005 148 plusmn 165 119875 gt 05


4 (V4) Althaea officinalisL 9755 plusmn 3360 05 gt 119875 gt 01 148 plusmn 330 119875 gt 05

5 (V5) Bauhinia variegata L 1972 plusmn 300 119875 gt 0001 83 plusmn 676 119875 gt 05

6 (V6) Brassica nigra (L) W D J Koch 8555 plusmn 050 005 gt 119875 gt 002 90 plusmn 085 05 gt 119875 gt 01







13 (V12) Enicostemma hyssopifolium(Willd) I Verd 1615 plusmn 151 119875 gt 0001 985 plusmn 166 05 gt 119875 gt 01

14 (V13) Fagonia cretica L 1418 plusmn 1303 002 gt 119875 gt 001 11 plusmn 252 119875 gt 05

15 (V14) Leucas capitata Desf 783 plusmn 1002 05 gt 119875 gt 01 14 plusmn 080 119875 gt 05

16 (V15) Matthiola incana (L) W T Aiton 1428 plusmn 651 119875 gt 0001 08 plusmn 166 05 gt 119875 gt 01

17 (V16) Momordica charantia L 14755 plusmn 351 119875 gt 0001 156 plusmn 245 119875 gt 05

18 (V17) Nerium indicumMill 1268 plusmn 1203 002 gt 119875 gt 001 05 plusmn 165 05 gt 119875 gt 01

19 (V18) Ocimum sanctum L 1335 plusmn 1203 002 gt 119875 gt 001 123 plusmn 245 119875 gt 05

20 (V19) Pinus roxburghii Sarg 1050 plusmn 100 002 gt 119875 gt 001 08 plusmn 165 05 gt 119875 gt 01


22 (V21) Psoralea corylifolia L 11535 plusmn 05 119875 gt 0001 173 plusmn 250 05 gt 119875 gt 01


24 (V23) Rubia cordifolia L 1078 plusmn 1604 005 gt 119875 gt 002 66 plusmn 000 05 gt 119875 gt 01



27 (V26) Terminalia arjuna (Roxb exDC) Wight and Arn 7985 plusmn 1454 05 gt 119875 gt 01 66 plusmn 000 05 gt 119875 gt 01




763 plusmn 601 Select to compare 09 plusmn 085 Select to compare

effects are due to phospholipid hydrolysis or phospholipidcompeting bidingmechanismwith other coagulation factorsparticularly FXa or by both ways however it is very hardto pinpoint exact one [35] Anticoagulant response posed bycobra PLA

2(anticoagulant enzyme) may aggravate hepatic

injury as many anticoagulant agents cause liver damage thatare idiosyncratic in nature [36]

Cardiac injury particularly systolic heart arrest is one ofthewell-known toxicities related toNaja naja subspecies [30]In present study Pakistani cobra venom was found to release

two cystolic enzymes (LDH and CK-MB) that are sensitiveindicators of myocyte injury [37] It is due to the presenceof myotoxic PLA

2and other cardiotoxin(s) that are salient

features of cobra venom that are responsible for cellularnecrosis and cytotoxicity [38 39] Cytotoxic effect of Najanaja karachiensis venom may not be overlooked even whenantisera administration is late cause of toxic components tothe microvasculature and thrombus produced which poseshindrance in access of immunoglobulins to the site of snakebite [26 29 39]


0

10

20

30

40

50

60

70Se

rum

leve

l of u

rea a

nd cr

eatin

ine (

mg

dL)

UreaCreatinine

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

L

Rhaz

ya st

ricta

Dec

neRu

bia

cord

ifolia

L

Sapi

ndus

muk

oros

si G

aert

nSt

enol

obiu

m st

ans (

L) S

eem

Term

inal

ia a

rjuna

(Rox

b ex

DC

) Wig

ht an

d A

rnTr

ichod

esm

a in

dicu

m (L

) Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te

Various antidotes tested (100mgkg)

Figure 2 Comparison of various medicinal plant extracts with reference standard antivenom in neutralization of elevated serum urea andcreatinine level posed by Naja naja karachiensis venom in rabbits

Snake venom has been responsible for detrimental effectsto the renal tissues [40] Likewise Naja naja krachiensisvenomwas found to cause severe renal damage by significantrise in serum urea and creatinine levels Indeed phospho-lipases enzymes are responsible for the increase in vascularpermeability with hemorrhagic effects to the vital tissues inthe victims Subsequently numerous lesions are producedrelated to the glomerular membrane and renal tubules eitherinterstitial or vascular [29 41 42] Presence of lymphocytes(white blood cells) and oedema in the cortical as well asmedullary regions of renal tubules further confirmed theidea of renal damage (data has not shown) as reportedpreviously with different snake venoms like Hemiscorpiuslepturus [26 43] Apart of it pharmacokinetic studies ofNaja naja karachiensis venom with short lived radioisotope99mTc confirmed that kidneys and urinary bladder are themost saturated organs (gt70) after intravenous injection inexperimental rabbits (unpublished data by our group)

Medicinal plants of Pakistan are used to inhibit snakevenom (PLA

2) enzymes [6] Due to this effect present

study was designed to select twenty-eight medicinal plantsof Pakistan to test their potentials as an antidote againsttoxicities produced by Naja naja karachiensis venom It

was fascinating that extract of Stenolobium stans (L) Seemshowed significant neutralization compared to that of refer-ence standard (antisera) as reported previously by Asad etal for inhibition of phospholipases A

2anticoagulant activity

[6 44] Present study indicated that extract of Stenolobiumstans (L) Seem possesses an endogenous inhibitor(s) tonullify venom (PLA

2) induced toxicities Extracts of these

plants material are routinely used in Pakistan by simpleapplication in the form of paste to the affected area [45]This practice provides effective first aid treatment as tinymolecules of an antidote diffuse favorably at the site of snakebite before hospitalization and abrogated the spreading oftoxins [39] It is owing to the various secondary metaboliteslike phenols flavonoids terpenoids xanthenes quinonoidsand so forth as reported earlier to mask various enzymaticactions of cobra venom [6 23] Indeed secondarymetabolitespose hindrance in binding of different snake venom enzymesto their potential targets therefore antidotal effect evokedOther plants extract were not proved significantly effectiveto neutralize cobra venom therefore cannot be declareduseful plants in venom therapy It is the need of the time toisolate lethal component(s) of cobra venom attributed to itsmajor toxicities Furthermore characterization of antivenom


1000

0

2000CK

-MB

(UL

)S

erum

leve

l of L

DH

LDHCK-MB

0-Al

bizi

a leb

beck

(L)

Bent

hAl

lium

cepa

L

Alliu

m sa

tivum

L

Alth

aea

officin

alis

LBa

uhin

ia va

riega

ta L

Br

assic

a ni

gra

(L)

W D

J K

och

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Cedr

us d

eoda

ra (R

oxb

ex D

Don

) G D

onCi

trus l

imon

(L)

Burm

f

Citru

llus c

oloc

ynth

is (L

) Sc

hrad

Cum

inum

cym

inum

L

Enico

stem

ma

hysso

pifo

lium

(Will

d) I

Ver

dFa

goni

a cr

etica

L

Leuc

as ca

pita

ta D

esf

Mat

thio

la in

cana

(L)

W T

Aito

nM

omor

dica

char

antia

L

Neriu

m in

dicu

m M

illO

cimum

sanc

tum

L

Pinu

s rox

burg

hii S

arg

Pista

cia in

tege

rrim

a J

L S

tew

art

Psor

alea

cory

lifol

ia L

Rhaz

ya st

ricta

Dec

ne

Rubi

a co

rdifo

lia L

Sapi

ndus

muk

oros

si G

aert

n

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C)

Trich

odes

ma

indi

cum

(L)

Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te

Various antivenoms tested (100mgkg)

Wig

ht an

d A

rn

Figure 3 Comparison of various medicinal plant extracts with reference standard antisera in neutralization of LDH and CK-MB levelselevated by Naja naja karachiensis venom in rabbits

compound(s) from medicinal plant extracts would be worthfull for complete and effective treatment of snake bite in thefuture

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgments

The authors are cordially thankful to Dr Khan MuhammadSajid (Deputy Chief Scientist MINAR) and Israr Ahmad(Radiopharmacist MINAR) for their valuable suggestionsSpecial thanks are due to Director COMSATS Institute ofInformationTechnologyAbbottabad Pakistan for the grant ofstudy leave to conduct research inMultan Institute of NuclearMedicine and Radiotherapy (MINAR) Nishtar HospitalMultan Pakistan

References

[1] WWuster ldquoThe cobras of the genus Naja in IndiardquoHamadryadvol 23 pp 15ndash32 1998

[2] P E P Deraniyagala ldquoThe taxonomy of the cobras of south-eastern Asia part 2rdquo Spolia Zeylanica vol 29 pp 205ndash232 1961

[3] T M Davidson S Schafer and J Killfoil ldquoCobrasrdquo Wildernessand Environmental Medicine vol 6 no 2 pp 203ndash219 1995

[4] M H H B Asad M T Razi T Khan et al ldquoCoagulopathies inNaja naja karachiensis (black Pakistan cobra) bites and its effect

on coagulation tests upon storage of platelet poor plasmardquo ActaPoloniae Pharmaceutica vol 69 pp 1031ndash1034 2012

[5] R C Hider E Karlsson and S Namiranian ldquoSeparation andpurification of toxins from snake venomsrdquo in InternationalEncyclopedia of Pharmacology andTherapeutics 11 A L HarveyEd section 134-snake toxins pp 1ndash34 Pergamon Press NewYork NY USA 1991

[6] M H H B Asad M T Razi Durr-e-Sabih et al ldquoAnti-venompotential of Pakistani medicinal plants inhibition of anticoagu-lation activity of Naja naja karachiensis toxinrdquo Current Sciencevol 105 pp 1419ndash1424 2013

[7] D Mebs ldquoToxicity in animals Trends in evolutionrdquo Toxiconvol 39 no 1 pp 87ndash96 2001

[8] S D Aird ldquoOphidian envenomation strategies and the role ofpurinesrdquo Toxicon vol 40 no 4 pp 335ndash393 2002

[9] T Chijiwa Y Yamaguchi T Ogawa et al ldquoInterisland evolutionofTrimeresurus flavoviridis venomphospholipaseA

2isozymesrdquo

Journal of Molecular Evolution vol 56 no 3 pp 286ndash293 2003[10] B Lomonte Y Angulo and L Calderon ldquoAn overview of lysine-

49 phospholipase A2 myotoxins from crotalid snake venomsand their structural determinants of myotoxic actionrdquo Toxiconvol 42 no 8 pp 885ndash901 2003

[11] B LDhananjaya B S Vishwanath andC JMDrsquoSouza ldquoSnakevenom nucleases nucleotidases and phosphomonoesterasesrdquoin Handbook of Venoms and Toxins of Reptiles S P MackessyEd pp 155ndash171 CRC Press Boca Raton Fla USA 2009

[12] S PMackessy ldquoPhosphodiesterases ribonucleases anddeoxyri-bonucleasesrdquo in Enzymes from Snake Venom G S Bailey Edpp 361ndash404 Alaken Fort Collins Colo USA 1998

[13] B L Dhananjaya A Nataraju R Rajesh et al ldquoAnticoagu-lant effect of Naja naja venom 5∘nucleotidase demonstration


through the use of novel specific inhibitor vanillic acidrdquoToxicon vol 48 no 4 pp 411ndash421 2006

[14] B L Dhananjaya and C J M DrsquoSouza ldquoThe Pharmacologicalrole of phosphatases (acid and alkaline phosphomonoesterases)in snake venoms related to release of purinesmdasha multitoxinrdquoBasic and Clinical Pharmacology and Toxicology vol 108 no 2pp 79ndash83 2011

[15] K S Girish D K Jagadeesha K B Rajeev and K KemparajuldquoSnake venom hyaluronidase an evidence for isoforms andextracellular matrix degradationrdquo Molecular and Cellular Bio-chemistry vol 240 no 1-2 pp 105ndash110 2002

[16] NH Tan and S Y Fung ldquoSnake venomL-amino acid oxidasesrdquoin Handbook of Venoms and Toxins of Reptiles S P MackessyEd pp 221ndash235 CRC Press Boca Raton Fla USA 2009

[17] D Mebs Venomous and Poisonous Animals A Handbookfor Biologists Toxicologists and Toxinologists Physicians andPharmacists CRC Press Boca Raton Fla USA 2002

[18] NAAbdoon andA J Fatani ldquoCorrelation between blood pres-sure cytokines and nitric oxide in conscious rabbits injectedwith Leiurus quinquestriatus quinquestriatus scorpion venomrdquoToxicon vol 54 no 4 pp 471ndash480 2009

[19] K S Latimer E A Mahaffey and K W Prasse Duncanand Prassersquos Veterinary Laboratory Medicine Clinical PathologyWiley-Blackwell New York NY USA 5th edition 2003

[20] J E Harkness P V Turner S V Woude and C L WhelerHarkness and Wagnerrsquos Biology and Medicine of Rabbits andRodents Wiley-Blackwell New York NY USA 5th edition2010

[21] F S Apple ldquoThe specificity of biochemical markers of cardiacdamage a problem solvedrdquo Clinical Chemistry and LaboratoryMedicine vol 37 no 11-12 pp 1085ndash1089 1999

[22] HO AlkadiM A Noman A K Al-Thobhani F S Al-Meklafiand Y A Rajarsquoa ldquoClinical and experimental evaluation of theeffect of Khat-induced myocardial infarctionrdquo Saudi MedicalJournal vol 23 no 10 pp 1195ndash1198 2002

[23] M H H B Asad G Murtaza S Siraj et al ldquoEnlisting the sci-entifically unnoticed medicinal plants of Pakistan as a source ofnovel therapeutic agents showing anti-venom activityrdquo AfricanJournal of Pharmacy and Pharmacology vol 5 no 20 pp 2292ndash2305 2011

[24] M H H B Asad D E Sabih B A Chaudhary et al ldquoAnti-hemolytic (anti-venom) activity of Pakistani medicinal plantsuponNaja naja karachiensis venominduced hemolysisrdquo Journalof Animal and Plant Sciences In press

[25] E B Ezenwanne and R E Ucheya ldquoA study of the serumconcentrations of some hepatic enzymes in doses of aqueousleaf extract of Vernonia amygdalina in rabbitsrdquo InternationalJournal of Animal and Veterinary Advances vol 4 pp 80ndash832012

[26] Z A Mirakabadi S M Khatoonabadi S H Teimourzadehand G H H Sabiri ldquoSerum enzymes studies in scorpion(Hemiscorpius lepturus) dose related envenomation in rabbitsrdquoArchives of Razi Institut vol 65 pp 83ndash89 2010

[27] C J Green J Knight S Precious and S Simpkin ldquoKetaminealone and combined with diazepam or xylazine in laboratoryanimals a 10 year experiencerdquo Laboratory Animals vol 15 no2 pp 163ndash170 1981

[28] S S Hasson A A Al-Jabri T A Sallam M S Al-Balushiand R A A Mothana ldquoAntisnake venom activity of Hibiscusaethiopicus L against Echis ocellatus and Naja n nigricollisrdquoJournal of Toxicology vol 2010 Article ID 837864 8 pages 2010

[29] M Tahir Razi M H H B Asad T Khan et al ldquoAnti-haemorrhagic potentials of Fagonia cretica against Naja najakarachiensis (black Pakistan cobra) venomrdquo Natural ProductResearch vol 25 no 20 pp 1902ndash1907 2011

[30] M Chethankumar and L Srinivas ldquoGangliosides as potentialinhibitors of Naja naja venom PLA2 (NV-PLA2) inducedhuman erythrocyte membrane damagerdquo African Journal ofBiochemistry Research vol 2 no 1 pp 8ndash14 2008

[31] T R Rahmy and K Z Hemmaid ldquoHistological and histochem-ical alterations in the liver following intramuscular injectionwith a sublethal dose of the Egyptian cobra venomrdquo Journal ofNatural Toxins vol 9 no 1 pp 21ndash32 2000

[32] B Adzu M S Abubakar K S Izebe D D Akumka and K SGamaniel ldquoEffect of Annona senegalensis rootbark extracts onNaja nigricotlis nigricotlis venom in ratsrdquo Journal of Ethnophar-macology vol 96 no 3 pp 507ndash513 2005

[33] M A Huffman ldquoAnimal self-medication and ethno-medicineexploration and exploitation of the medicinal properties ofplantsrdquo Proceedings of the Nutrition Society vol 62 no 2 pp371ndash381 2003

[34] B W Segelke D Nguyen R Chee N H Xuong and E ADennis ldquoStructures of two novel crystal forms ofNaja naja najaphospholipase A

2lackingCa2+ reveal trimeric packingrdquo Journal

of Molecular Biology vol 279 no 1 pp 223ndash232 1998[35] Q Lu JM Clemetson andK J Clemetson ldquoSnake venoms and

hemostasisrdquo Journal of Thrombosis and Haemostasis vol 3 no8 pp 1791ndash1799 2005

[36] S Ehrenforth J F Schenk and I Scharrer ldquoLiver damageinduced by coumarin anticoagulantsrdquo Seminars in Thrombosisand Hemostasis vol 25 no 1 pp 79ndash83 1999

[37] M Nandave S K Ojha S Joshi S Kumari and D SArya ldquoCardioprotective effect of Bacopa monneira againstisoproterenol-induced myocardial necrosis in ratsrdquo Interna-tional Journal of Pharmacology vol 3 no 5 pp 385ndash392 2007

[38] H V Patel A A Vyas K A Vyas et al ldquoHeparin and heparansulfate bind to snake cardiotoxin sulfated oligosaccharides asa potential target for cardiotoxin actionrdquo Journal of BiologicalChemistry vol 272 no 3 pp 1484ndash1492 1997

[39] S Yingprasertchai S Bunyasrisawat and K Ratanabanang-koon ldquoHyaluronidase inhibitors (sodium cromoglycate andsodium auro-thiomalate) reduce the local tissue damage andprolong the survival time of mice injected with Naja kaouthiaand Calloselasma rhodostoma venomsrdquo Toxicon vol 42 no 6pp 635ndash646 2003

[40] M Schneemann R Cathomas S T Laidlaw A M El NahasR D G Theakston and D A Warrell ldquoLife-threateningenvenoming by the Saharan horned viper (Cerastes cerastes)causingmicro-angiopathic haemolysis coagulopathy and acuterenal failure clinical cases and reviewrdquo QJMmdashMonthly Journalof the Association of Physicians vol 97 no 11 pp 717ndash727 2004

[41] J Meier and K Stocker ldquoEffects of snake venoms on hemosta-sisrdquoCritical Reviews inToxicology vol 21 no 3 pp 171ndash182 1991

[42] N Marsh D Gattullo P Pagliaro and G Losano ldquoThe gaboonviper Bitis gabonica hemorrhagic metabolic cardiovascularand clinical affects of the venomrdquo Life Sciences vol 61 no 8pp 763ndash769 1997

[43] M H Pipelzadeh A Jalali M Taraz R Pourabbas and AZaremirakabadi ldquoAn epidemiological and a clinical study onscorpionism by the Iranian scorpion Hemiscorpius lepturusrdquoToxicon vol 50 no 7 pp 984ndash992 2007

[44] M H H B Asad Durr-e-Sabih B A Choudary A F Asad GMurtaza and I Hussain ldquoCompensatory effects of medicinal


plants of Pakistan upon prolongation of coagulation assaysinduced by Naja naja karachiensis biterdquo Current Science vol106 pp 870ndash873 2014

[45] S R BaquarMedicinal and Poisonous Plants of Pakistan PrintasKarachi Pakistan 1st edition 1989

[46] I Archetti C Tittarelli M Cerioli R Brivio G Grilli and ALavazza ldquoSerum chemistry and hematology values in commer-cial rabbits preliminary data from industrial farms in northernItalyrdquo in Proceedings of the 9th World Rabbit Congress pp 1147ndash1152 Verona Italy 2008

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anatomy Research International

PeptidesInternational Journal of


Hindawi Publishing Corporation httpwwwhindawicom

International Journal of

Volume 2014

Zoology


Molecular Biology International

GenomicsInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014


BioinformaticsAdvances in

Marine BiologyJournal of



Signal TransductionJournal of


BioMed Research International

Evolutionary BiologyInternational Journal of



Biochemistry Research International

ArchaeaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Genetics Research International


Advances in

Virolog y

Hindawi Publishing Corporationhttpwwwhindawicom

Nucleic AcidsJournal of

Volume 2014

Stem CellsInternational



Enzyme Research



Microbiology


and increased creatinine and urea levels along with alteredconsciousness [3 4]

Indeed snake venom is a complex mixture of varioussizes of polypeptides [5 6] (lt15 kDa 5 to 10 kDa and10 to 150 kDa) carbohydrates lipids metal ions organicmolecules purines and amines [7 8] Snake bite enveno-mation has been attributed to pose drastic changes in thephysiology of the victims that could be accessed clinicallyby measuring various biochemical parameters Among toxiccomponents phospholipases A

2(cell destroying enzymes

cause edema lipolytic or myolytic) [9 10] phosphodi-esterases (nucleic acid degrading enzyme causes hypoten-sionshock) [11 12] 51015840 nucleotidases (digest the sugar moitiescausing the delay in coagulation) [13] alkaline phosphatases(hydrolyze phosphate esters nonspecifically cause multipletoxicities via adenosine generation) [14] hyaluronidases(spreading factor causes digestion necrosis and leakage ofblood vessels) [15] L-amino oxidases (deamination leads tocell damageapoptosis) [16] and proteases (hydrolyze variousproteins) [17] are included

Laboratory animals particularly rabbits have beenselected previously to monitor various biochemical changesrelated to liver heart and renal toxicities [18 19] Aspartateaminotransferase (GOTAST) and alanine aminotransferase(GPTALT) are surrogate markers for liver toxicities whilecreatine kinase isoenzyme (CK-MB) is used exclusively toaccess cardiac tissue damage [20 21] Elevated creatinine andurea levels are indicators of 75 renal damage [20] whereashigh level of lactate dehydrogenase (LDH) implies generaltoxicity related to the liver heart kidneys and skeletonmuscles [22]

Diverse immunological properties of different cobrashave fascinated protein chemists and other researchers tocarry out efforts for the development of new antidotes Dueto this reason for the first time venom from Naja najakarachiensis is selected to evaluate its toxicity in vivo andto search out effective as well as cheap treatment fromfolk herbal remedies Pakistan is a hub of medicinal plantswhere mostly rural communities rely on natural herbs totreat their problems of snake bite [6 23] It is thereforenecessary to evaluate scientifically their folklore claims asanti-snake venom in traditional system of medicine Dueto this reason various medicinal plants (Albizia lebbeck (L)Benth Allium cepa L Allium sativum L Althaea officinalisL Bauhinia variegata L Brassica nigra (L) W D J KochCalotropis procera (Aiton)WTAitonCedrus deodara (Roxbex D Don) G Don Citrullus colocynthis (L) Schrad Citruslimon (L) Burm f Cuminum cyminum L Enicostemahyssopifolium (Willd) I Verd Fagonia cretica L Leucascapitata DesfMatthiola incana (L) W T AitonMomordicacharantiaLNerium indicumMillOcimum sanctumL Pinusroxburghii Sarg Pistacia integerrima J L Stewart Psoraleacorylifolia L Rhazya stricta Decne Rubia cordifolia LSapindus mukorossi Gaertn Solanum xanthocarpum Schardand Wendle Stenolobium stans (L) Seem Terminalia arjuna(Roxb exDC)Wight andArnTrichodesma indicum (L) Smand Zingiber officinale Roscoe) were collected to test theirpotentials against toxicities induced byNaja naja karachiensisenvenomation (Table 1)

2 Material and Methods

21 Collection and Milking of Snake Venom Black Pakistanicobra snakes (Naja naja karachiensis) were collected fromCholistan desert located in southern Punjab province ofPakistan After collection they were properly identified by azoologist Venom from Naja naja karachiensis was collectedby pressing their glands below their eyes in low light environ-ment After collection it was lyophilized and stored in lightresistant container at 2∘C to 8∘C For further experimentsvenom was used in terms of its dry weight [6]

22 Collection and Preparation of Plant Extracts Medicinalplants were collected from different areas in Pakistan Aftercollection they were duly identified by expert botanist(Professor Dr Altaf Ahmad Dasti) and voucher specimenswere deposited in the herbarium of the Institute of Pure andApplied Biology Bahauddin Zakariya University MultanPakistan Complete description about evaluated medicinalplants is summarized in Table 1 One kilogram choppedplant material was soaked in 5 L of methanol as solvent inextraction bottlesThe homogenates were kept for a period ofa month at optimum temperature After filtration filtrate wasevaporated by using water bath and extracts were weighedand stored for further experimentation [24]

23 Experimental Animals Seventy-one healthy growingmale rabbits (1 plusmn 05 kg) were selected for this study aftergetting permission from local ethical committee Animalswere acclimatized for a week in the laboratory bymaintainingtheir standards for chow water and light Subsequently theywere divided into various groups in different cages suchthat experimental rabbits in group I were used for baselinemeasurements of various biochemical parameters Animalsbelonging to groups II and III were evaluated for differentdoses of cobra venom while group IV was served as controlGroup V was redivided into twenty-nine groups such thateach subgroup (V1ndashV29) was assigned to a single medicinalplant extract [25]

24 In Vivo Antivenom Activity of Medicinal Plant ExtractsVenom from Naja naja karachiensis (400 120583gkg and800 120583gkg) was injected subcutaneously to evaluate itstoxicity to the heart liver and kidneys Before injectionof venom experimental animals were anaesthetizedby administration of ketamine (50mgkg) To determineantivenomactivity of various plantsrsquo extract they (100mgkg)were incubated (at 37∘C for 30 minutes) with fixed amountof venom (800120583gkg) before injection while saline was usedas control [26ndash28]

25 Biochemical Assays For serum analysis of various bio-chemical parameters blood was collected from marginal earartery by the use of hypodermic syringe needle after 3 hoursof envenomation [25] Separated serumwas tested for alanineaminotransferase (GPTALT) aspartate aminotransferase(GOTAST) urea creatinine creatine kinase isoenzyme MB(CK-MB) and lactate dehydrogenase (LDH) by the use of



tionfore

valuated


folklore

evidencesa

santivenom

Srnum

ber

Botanicaln

ameo

fmedicinalplants

Family

Partused


Reference

1Albizialeb

beck

(L)Be

nth

Fabaceae

Seed

Carboh


acidand

different

aminoacids

[6]

2Alliu

mcepa

LAmaryllid

aceae

Bulb

11gcarboh

ydrates12

gproteins06gfib

ersandH

2Ocontent(868g)10

0gof

material

[6]

3Alliu

msativ

umL

Amaryllid

aceae

Bulb



ates2

mercapto-L-cyste

ines


lysaccharid

essativin

Iand

sativ

inIIand

glycosides

ofkaem

pferol

[6]

4Althaeaoffi

cinalisL

Malvaceae

Root

37sta


oidspheno

licacidsasparagines


tyric

acid

[6]

5Ba

uhiniavarie

gata

LFabaceae

Root

Tann

insfatty


egums120573-sito

sterol57-dehydroxy

and57-dimetho

xy-flavanon

e-4-0-a-L-rham

nopyrano

syl-120573

-Dglucop

yranosides

[6]

6Brassicanigra(L)WD

JK

och

Brassic

aceae

Seed

Essentialoilsin

igrin

andglucoside

[6]

7Ca

lotro

pisp

rocera

(Aito

n)WTA

iton

Apocyn

aceae

Exud

ates

andflo

wer

Resin

stann

inscalotro

pin


calotoxin

andcalactin

[6]

8Ce

drus

deodara(Roxbex

DD

on)G

Don

Pinaceae

Bark

Taxifolin

dew

ardioldew

arenegumascorbica


cholesterin

allo


dihydrod


olessentia

loiliso

centdaroland

dihydrom

yricetin

[6]

9Citru

slim

on(L)Bu

rmf

Rutaceae

Fruit


sided-x-pinene

camph

ened-lim

onenelin

aloo

lichangin


sideno

milinica

cidandessentialoil

[6]

10Citru


Cucurbita

ceae

Fruit


alcoho

lph



oilcitbittoland

sapo

nins

[6]

11Cu

minum

cyminum

LAp

iaceae

Seed


oilcon

tain

sminaldehyde13-p-m

enthadien-7-aland

14-p-m

enthadien-7-al

[6]

12En

icoste

mahysso

pifoliu

m(W

illd)IV

erd

Gentia

naceae

Who

leplant

Sapo

narin

isovetexin

sylysw

ertin

betulinswertia

marinapigenin

genk

wanin

erythrocentaurinesw

ertio

sideiso


swertisin

[6]

13Fagoniacretica

LZy

goph

yllaceae

Leaves

Ursolicacidpinito

lnahagenin

sapo

ninglycosidessapon

in-Iandsapo

nin-II

docosyld

ocosanoatefro

mn-hexane

extractanddifferent

proteins

from

aqueou

sextract

[6]

14Leucas

capitataDesf

Lamiaceae

Who

leplant

Alkaloidas

wellase

ssentia

loil

[6]

15Matthiolaincana

(L)WTA

iton

Brassic

aceae

Seeds

Oilric

hin

chloroph

yllsabNPK

and

Na120574-lino

lenica

cidandcaroteno

ids

Sulfo

raph

eneisa

nim

portantcom

ponent

[6]

16Mom

ordica

charantia

LCu

curbita

ceae

Fruit

Caroteno

idsmom

orcharasides

AandB

glucosidesstig

mastadien-3-beta-ol

squalenem


ordicinesI

andIIstig

masterolvicine

cucurbitane

triterpenoidsm

omordicosid

escycloeucaleno

ltaraxerol

spinasterollo


gen

24-m

ethylencycloarteno

land

phenylprop

anoids

[6]

17Ne

rium

indicum

Mill

Apocyn

aceae

Root

andleaves

Nerioderin

neriodo

rinkarabinand

odorin

[6]

18Ocim

umsanctum

LLamiaceae

Who

leplant

Essentialoils

arefou

ndric

hin

32

carvacrol713eugeno

l17

caryop

hyllene



[6]


Table1Con

tinued

Srnum

ber

Botanicaln

ameo

fmedicinalplants

Family

Partused


Reference

19Pinu

sroxburghiiSarg

Pinaceae

Oleoresin

Careen120572


ngifo

lenelon

gifoleneand

long

icyclene

[6]

20Pista

ciaintegerrim

aJLStewart

Anacardiaceae

Galls

13essentialoilric

hin

camph

enecineoleA-

terpineolA-

pinenearomadendrene

caprylicacidand

d-lim

onenea

bund

antingalls

[6]

21Psoralea

corylifoliaL

Fabaceae

Seeds

Limon

enelin

aloo



rpineol

corylid

inn

eobavaiso

flavonebavachinin

isobavachin120572


stigmasterolbaku

chioltraincon


eiso

neob

avachalcon

epsoralenpsoralid

inraffi

nosecorylifo

linincorylifo

leanand

corylifolin

[6]

22Rh

azya

strictaDecne

Apocyn

aceae

Leaves

Enzymes

(NADPH

depend

ent)

glycosides

(rob

lnin3-7-rhamno

sidea

ndiso

rham

netin

-3-7-rhamno

side)alkaloid(sew

arine)and

triterpenes

(ursolicacid

Mgqu

inateand120573-sito

sterol)alon

gwith

flavono

idsrhazianosides

AandB

[6]

23Ru

biacordifolia

LRu

biaceae

Stem

Pseudo

purpurinxanthop

urpu

rinpurpu

rinm

unjistin

alizarinand

mun

jistin

are

foun

dwith

theirg

lycosid

es

[6]

24Sapind

usmukorossiGaertn

Sapind

aceae

Fruit120573-Sito

sterolsapind

osideA

sapindo

sideB


inand

emarginatosid

e[6]

25Stenolob

ium

stans

(L)Seem

Bign

oniaceae

Root120573-C

arotene120573-sito


olem

etabolizingenzymes

phenolicacidsoleano

licacidtriterpeno

idsursolic

acidind

ole-oxygenaseand

luteinzeaxanthin

[6]

26Term

inaliaarjuna

(Roxbex

DC)W

ight

andArn

Com

bretaceae

Bark120573-Sito

sterolarjuno

licacidtom

entosic

acidellagica


arjuninecalcium

saltsaluminium

andmagnesiu


redu

cing


l)andalactone

[6]

27Trich

odesmaindicum

(L)Sm

Boraginaceae

Who

leplantSeedso

ilisric

hin

linoleicoleicste

aricpalmiticandlin

olenicacidsAp

arto

fit



icacid

ethyleste

rsare

foun

d[6]

28Zingiberoffi

cinaleR

oscoe

Zing

iberaceae

Rhizom

eD-C


moxalatecamph

enecitralbo

rneolsin

giberin


ma-bisabo

lenegingeroland

120573-phelland

rene

23



eforea

ndaft

ersnakev

enom

administratio

nin

different

experim

entalgroup

sofrabbits

Toxicitydeterm

ined

Markersof

snake

veno

mtoxicity

Group

Ibaseline

measurements

(meanplusmnSE

M)

Group

IIandIIIv

enom

injection

Group

IVnegativ

econ

trol

(meanplusmnSE

M)

Normalreference

values

repo

rted

References

04m

gkg

(meanplusmnSE

M)

08m

gkg

(meanplusmnSE

M)

Liver

GPT

ALT

(52plusmn346

)UL

(72plusmn470)U

L01gt119875gt005

(86plusmn50)

UL

005gt119875gt002

(52plusmn348)U

L(48ndash80)U

L[19

]

GOTAST

(65plusmn657)U

L(157plusmn2424)

UL

01gt119875gt005

(251plusmn182)U

L001gt119875gt0001

(67plusmn321)U

L(14

ndash113)U

L[19

]

Kidn

eys

Urea

(28plusmn17

3)mgdL

(42plusmn308)m

gdL

005gt119875gt002

(576plusmn384)m

gdL

002gt119875gt001

(28plusmn033)m

gdL

(10ndash

28)m

gdL

[26]

Creatin

ine

(10plusmn0313)

mgdL

(174plusmn003)m

gdL

001gt119875gt0001

(21plusmn010)m

gdL

002gt119875gt001

(1plusmn006)m

gdL

(05ndash25)m

gdL

[26]

Heart

CK-M

B(132plusmn20)

UL

(21plusmn

15)U

L005gt119875gt002

(77plusmn1122)

UL

005gt119875gt002

(13plusmn056)U

L(lt25)U

Llowast

[2021]

LDH

(714plusmn318)U

L(206

4plusmn1598)

UL

119875lt0001

(2562plusmn2514

)UL

119875≪0001

(720plusmn470)U

L(559ndash2077)

UL

[46]

lowastCK

-MBactiv

ityislessthan

2in

healthyrabbitshow

everitisu

sually10ndash30

oftotalC

Kactiv

ity


0

50

100

150

200

250

300Se

rum

leve

l of G

PTG

OT

(UL

)

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

LRh

azya

stric

ta D

ecne

Rubi

a co

rdifo

lia L

Sa

pind

us m

ukor

ossi

Gae

rtn

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C) W

ight

and

Arn

Trich

odes

ma

indi

cum

(L)

SmZi

ngib

er o

fficin

ale R

osco

eRe

fere

nce s

tand

ard

anti

dote

GPT levelGOT level





3 Results







UL(mean plusmn SEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment














0051685 plusmn 757 05 gt 119875 gt 01






005














compare



4 Discussion






119875 valuecomment


119875 valuecomment
































compare







2is also found





UL (mean plusmnSEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment








































0

10

20

30

40

50

60

70Se

rum

leve

l of u

rea a

nd cr

eatin

ine (

mg

dL)

UreaCreatinine

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

L

Rhaz

ya st

ricta

Dec

neRu

bia

cord

ifolia

L

Sapi

ndus

muk

oros

si G

aert

nSt

enol

obiu

m st

ans (

L) S

eem

Term

inal

ia a

rjuna

(Rox

b ex

DC

) Wig

ht an

d A

rnTr

ichod

esm

a in

dicu

m (L

) Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te













1000

0

2000CK

-MB

(UL

)S

erum

leve

l of L

DH

LDHCK-MB

0-Al

bizi

a leb

beck

(L)

Bent

hAl

lium

cepa

L

Alliu

m sa

tivum

L

Alth

aea

officin

alis

LBa

uhin

ia va

riega

ta L

Br

assic

a ni

gra

(L)

W D

J K

och

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Cedr

us d

eoda

ra (R

oxb

ex D

Don

) G D

onCi

trus l

imon

(L)

Burm

f

Citru

llus c

oloc

ynth

is (L

) Sc

hrad

Cum

inum

cym

inum

L

Enico

stem

ma

hysso

pifo

lium

(Will

d) I

Ver

dFa

goni

a cr

etica

L

Leuc

as ca

pita

ta D

esf

Mat

thio

la in

cana

(L)

W T

Aito

nM

omor

dica

char

antia

L

Neriu

m in

dicu

m M

illO

cimum

sanc

tum

L

Pinu

s rox

burg

hii S

arg

Pista

cia in

tege

rrim

a J

L S

tew

art

Psor

alea

cory

lifol

ia L

Rhaz

ya st

ricta

Dec

ne

Rubi

a co

rdifo

lia L

Sapi

ndus

muk

oros

si G

aert

n

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C)

Trich

odes

ma

indi

cum

(L)

Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te


Wig

ht an

d A

rn





Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology



tionfore

valuated


folklore

evidencesa

santivenom

Srnum

ber

Botanicaln

ameo

fmedicinalplants

Family

Partused


Reference

1Albizialeb

beck

(L)Be

nth

Fabaceae

Seed

Carboh


acidand

different

aminoacids

[6]

2Alliu

mcepa

LAmaryllid

aceae

Bulb

11gcarboh

ydrates12

gproteins06gfib

ersandH

2Ocontent(868g)10

0gof

material

[6]

3Alliu

msativ

umL

Amaryllid

aceae

Bulb



ates2

mercapto-L-cyste

ines


lysaccharid

essativin

Iand

sativ

inIIand

glycosides

ofkaem

pferol

[6]

4Althaeaoffi

cinalisL

Malvaceae

Root

37sta


oidspheno

licacidsasparagines


tyric

acid

[6]

5Ba

uhiniavarie

gata

LFabaceae

Root

Tann

insfatty


egums120573-sito

sterol57-dehydroxy

and57-dimetho

xy-flavanon

e-4-0-a-L-rham

nopyrano

syl-120573

-Dglucop

yranosides

[6]

6Brassicanigra(L)WD

JK

och

Brassic

aceae

Seed

Essentialoilsin

igrin

andglucoside

[6]

7Ca

lotro

pisp

rocera

(Aito

n)WTA

iton

Apocyn

aceae

Exud

ates

andflo

wer

Resin

stann

inscalotro

pin


calotoxin

andcalactin

[6]

8Ce

drus

deodara(Roxbex

DD

on)G

Don

Pinaceae

Bark

Taxifolin

dew

ardioldew

arenegumascorbica


cholesterin

allo


dihydrod


olessentia

loiliso

centdaroland

dihydrom

yricetin

[6]

9Citru

slim

on(L)Bu

rmf

Rutaceae

Fruit


sided-x-pinene

camph

ened-lim

onenelin

aloo

lichangin


sideno

milinica

cidandessentialoil

[6]

10Citru


Cucurbita

ceae

Fruit


alcoho

lph



oilcitbittoland

sapo

nins

[6]

11Cu

minum

cyminum

LAp

iaceae

Seed


oilcon

tain

sminaldehyde13-p-m

enthadien-7-aland

14-p-m

enthadien-7-al

[6]

12En

icoste

mahysso

pifoliu

m(W

illd)IV

erd

Gentia

naceae

Who

leplant

Sapo

narin

isovetexin

sylysw

ertin

betulinswertia

marinapigenin

genk

wanin

erythrocentaurinesw

ertio

sideiso


swertisin

[6]

13Fagoniacretica

LZy

goph

yllaceae

Leaves

Ursolicacidpinito

lnahagenin

sapo

ninglycosidessapon

in-Iandsapo

nin-II

docosyld

ocosanoatefro

mn-hexane

extractanddifferent

proteins

from

aqueou

sextract

[6]

14Leucas

capitataDesf

Lamiaceae

Who

leplant

Alkaloidas

wellase

ssentia

loil

[6]

15Matthiolaincana

(L)WTA

iton

Brassic

aceae

Seeds

Oilric

hin

chloroph

yllsabNPK

and

Na120574-lino

lenica

cidandcaroteno

ids

Sulfo

raph

eneisa

nim

portantcom

ponent

[6]

16Mom

ordica

charantia

LCu

curbita

ceae

Fruit

Caroteno

idsmom

orcharasides

AandB

glucosidesstig

mastadien-3-beta-ol

squalenem


ordicinesI

andIIstig

masterolvicine

cucurbitane

triterpenoidsm

omordicosid

escycloeucaleno

ltaraxerol

spinasterollo


gen

24-m

ethylencycloarteno

land

phenylprop

anoids

[6]

17Ne

rium

indicum

Mill

Apocyn

aceae

Root

andleaves

Nerioderin

neriodo

rinkarabinand

odorin

[6]

18Ocim

umsanctum

LLamiaceae

Who

leplant

Essentialoils

arefou

ndric

hin

32

carvacrol713eugeno

l17

caryop

hyllene



[6]


Table1Con

tinued

Srnum

ber

Botanicaln

ameo

fmedicinalplants

Family

Partused


Reference

19Pinu

sroxburghiiSarg

Pinaceae

Oleoresin

Careen120572


ngifo

lenelon

gifoleneand

long

icyclene

[6]

20Pista

ciaintegerrim

aJLStewart

Anacardiaceae

Galls

13essentialoilric

hin

camph

enecineoleA-

terpineolA-

pinenearomadendrene

caprylicacidand

d-lim

onenea

bund

antingalls

[6]

21Psoralea

corylifoliaL

Fabaceae

Seeds

Limon

enelin

aloo



rpineol

corylid

inn

eobavaiso

flavonebavachinin

isobavachin120572


stigmasterolbaku

chioltraincon


eiso

neob

avachalcon

epsoralenpsoralid

inraffi

nosecorylifo

linincorylifo

leanand

corylifolin

[6]

22Rh

azya

strictaDecne

Apocyn

aceae

Leaves

Enzymes

(NADPH

depend

ent)

glycosides

(rob

lnin3-7-rhamno

sidea

ndiso

rham

netin

-3-7-rhamno

side)alkaloid(sew

arine)and

triterpenes

(ursolicacid

Mgqu

inateand120573-sito

sterol)alon

gwith

flavono

idsrhazianosides

AandB

[6]

23Ru

biacordifolia

LRu

biaceae

Stem

Pseudo

purpurinxanthop

urpu

rinpurpu

rinm

unjistin

alizarinand

mun

jistin

are

foun

dwith

theirg

lycosid

es

[6]

24Sapind

usmukorossiGaertn

Sapind

aceae

Fruit120573-Sito

sterolsapind

osideA

sapindo

sideB


inand

emarginatosid

e[6]

25Stenolob

ium

stans

(L)Seem

Bign

oniaceae

Root120573-C

arotene120573-sito


olem

etabolizingenzymes

phenolicacidsoleano

licacidtriterpeno

idsursolic

acidind

ole-oxygenaseand

luteinzeaxanthin

[6]

26Term

inaliaarjuna

(Roxbex

DC)W

ight

andArn

Com

bretaceae

Bark120573-Sito

sterolarjuno

licacidtom

entosic

acidellagica


arjuninecalcium

saltsaluminium

andmagnesiu


redu

cing


l)andalactone

[6]

27Trich

odesmaindicum

(L)Sm

Boraginaceae

Who

leplantSeedso

ilisric

hin

linoleicoleicste

aricpalmiticandlin

olenicacidsAp

arto

fit



icacid

ethyleste

rsare

foun

d[6]

28Zingiberoffi

cinaleR

oscoe

Zing

iberaceae

Rhizom

eD-C


moxalatecamph

enecitralbo

rneolsin

giberin


ma-bisabo

lenegingeroland

120573-phelland

rene

23



eforea

ndaft

ersnakev

enom

administratio

nin

different

experim

entalgroup

sofrabbits

Toxicitydeterm

ined

Markersof

snake

veno

mtoxicity

Group

Ibaseline

measurements

(meanplusmnSE

M)

Group

IIandIIIv

enom

injection

Group

IVnegativ

econ

trol

(meanplusmnSE

M)

Normalreference

values

repo

rted

References

04m

gkg

(meanplusmnSE

M)

08m

gkg

(meanplusmnSE

M)

Liver

GPT

ALT

(52plusmn346

)UL

(72plusmn470)U

L01gt119875gt005

(86plusmn50)

UL

005gt119875gt002

(52plusmn348)U

L(48ndash80)U

L[19

]

GOTAST

(65plusmn657)U

L(157plusmn2424)

UL

01gt119875gt005

(251plusmn182)U

L001gt119875gt0001

(67plusmn321)U

L(14

ndash113)U

L[19

]

Kidn

eys

Urea

(28plusmn17

3)mgdL

(42plusmn308)m

gdL

005gt119875gt002

(576plusmn384)m

gdL

002gt119875gt001

(28plusmn033)m

gdL

(10ndash

28)m

gdL

[26]

Creatin

ine

(10plusmn0313)

mgdL

(174plusmn003)m

gdL

001gt119875gt0001

(21plusmn010)m

gdL

002gt119875gt001

(1plusmn006)m

gdL

(05ndash25)m

gdL

[26]

Heart

CK-M

B(132plusmn20)

UL

(21plusmn

15)U

L005gt119875gt002

(77plusmn1122)

UL

005gt119875gt002

(13plusmn056)U

L(lt25)U

Llowast

[2021]

LDH

(714plusmn318)U

L(206

4plusmn1598)

UL

119875lt0001

(2562plusmn2514

)UL

119875≪0001

(720plusmn470)U

L(559ndash2077)

UL

[46]

lowastCK

-MBactiv

ityislessthan

2in

healthyrabbitshow

everitisu

sually10ndash30

oftotalC

Kactiv

ity


0

50

100

150

200

250

300Se

rum

leve

l of G

PTG

OT

(UL

)

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

LRh

azya

stric

ta D

ecne

Rubi

a co

rdifo

lia L

Sa

pind

us m

ukor

ossi

Gae

rtn

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C) W

ight

and

Arn

Trich

odes

ma

indi

cum

(L)

SmZi

ngib

er o

fficin

ale R

osco

eRe

fere

nce s

tand

ard

anti

dote

GPT levelGOT level





3 Results







UL(mean plusmn SEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment














0051685 plusmn 757 05 gt 119875 gt 01






005














compare



4 Discussion






119875 valuecomment


119875 valuecomment
































compare







2is also found





UL (mean plusmnSEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment








































0

10

20

30

40

50

60

70Se

rum

leve

l of u

rea a

nd cr

eatin

ine (

mg

dL)

UreaCreatinine

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

L

Rhaz

ya st

ricta

Dec

neRu

bia

cord

ifolia

L

Sapi

ndus

muk

oros

si G

aert

nSt

enol

obiu

m st

ans (

L) S

eem

Term

inal

ia a

rjuna

(Rox

b ex

DC

) Wig

ht an

d A

rnTr

ichod

esm

a in

dicu

m (L

) Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te













1000

0

2000CK

-MB

(UL

)S

erum

leve

l of L

DH

LDHCK-MB

0-Al

bizi

a leb

beck

(L)

Bent

hAl

lium

cepa

L

Alliu

m sa

tivum

L

Alth

aea

officin

alis

LBa

uhin

ia va

riega

ta L

Br

assic

a ni

gra

(L)

W D

J K

och

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Cedr

us d

eoda

ra (R

oxb

ex D

Don

) G D

onCi

trus l

imon

(L)

Burm

f

Citru

llus c

oloc

ynth

is (L

) Sc

hrad

Cum

inum

cym

inum

L

Enico

stem

ma

hysso

pifo

lium

(Will

d) I

Ver

dFa

goni

a cr

etica

L

Leuc

as ca

pita

ta D

esf

Mat

thio

la in

cana

(L)

W T

Aito

nM

omor

dica

char

antia

L

Neriu

m in

dicu

m M

illO

cimum

sanc

tum

L

Pinu

s rox

burg

hii S

arg

Pista

cia in

tege

rrim

a J

L S

tew

art

Psor

alea

cory

lifol

ia L

Rhaz

ya st

ricta

Dec

ne

Rubi

a co

rdifo

lia L

Sapi

ndus

muk

oros

si G

aert

n

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C)

Trich

odes

ma

indi

cum

(L)

Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te


Wig

ht an

d A

rn





Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


Table1Con

tinued

Srnum

ber

Botanicaln

ameo

fmedicinalplants

Family

Partused


Reference

19Pinu

sroxburghiiSarg

Pinaceae

Oleoresin

Careen120572


ngifo

lenelon

gifoleneand

long

icyclene

[6]

20Pista

ciaintegerrim

aJLStewart

Anacardiaceae

Galls

13essentialoilric

hin

camph

enecineoleA-

terpineolA-

pinenearomadendrene

caprylicacidand

d-lim

onenea

bund

antingalls

[6]

21Psoralea

corylifoliaL

Fabaceae

Seeds

Limon

enelin

aloo



rpineol

corylid

inn

eobavaiso

flavonebavachinin

isobavachin120572


stigmasterolbaku

chioltraincon


eiso

neob

avachalcon

epsoralenpsoralid

inraffi

nosecorylifo

linincorylifo

leanand

corylifolin

[6]

22Rh

azya

strictaDecne

Apocyn

aceae

Leaves

Enzymes

(NADPH

depend

ent)

glycosides

(rob

lnin3-7-rhamno

sidea

ndiso

rham

netin

-3-7-rhamno

side)alkaloid(sew

arine)and

triterpenes

(ursolicacid

Mgqu

inateand120573-sito

sterol)alon

gwith

flavono

idsrhazianosides

AandB

[6]

23Ru

biacordifolia

LRu

biaceae

Stem

Pseudo

purpurinxanthop

urpu

rinpurpu

rinm

unjistin

alizarinand

mun

jistin

are

foun

dwith

theirg

lycosid

es

[6]

24Sapind

usmukorossiGaertn

Sapind

aceae

Fruit120573-Sito

sterolsapind

osideA

sapindo

sideB


inand

emarginatosid

e[6]

25Stenolob

ium

stans

(L)Seem

Bign

oniaceae

Root120573-C

arotene120573-sito


olem

etabolizingenzymes

phenolicacidsoleano

licacidtriterpeno

idsursolic

acidind

ole-oxygenaseand

luteinzeaxanthin

[6]

26Term

inaliaarjuna

(Roxbex

DC)W

ight

andArn

Com

bretaceae

Bark120573-Sito

sterolarjuno

licacidtom

entosic

acidellagica


arjuninecalcium

saltsaluminium

andmagnesiu


redu

cing


l)andalactone

[6]

27Trich

odesmaindicum

(L)Sm

Boraginaceae

Who

leplantSeedso

ilisric

hin

linoleicoleicste

aricpalmiticandlin

olenicacidsAp

arto

fit



icacid

ethyleste

rsare

foun

d[6]

28Zingiberoffi

cinaleR

oscoe

Zing

iberaceae

Rhizom

eD-C


moxalatecamph

enecitralbo

rneolsin

giberin


ma-bisabo

lenegingeroland

120573-phelland

rene

23



eforea

ndaft

ersnakev

enom

administratio

nin

different

experim

entalgroup

sofrabbits

Toxicitydeterm

ined

Markersof

snake

veno

mtoxicity

Group

Ibaseline

measurements

(meanplusmnSE

M)

Group

IIandIIIv

enom

injection

Group

IVnegativ

econ

trol

(meanplusmnSE

M)

Normalreference

values

repo

rted

References

04m

gkg

(meanplusmnSE

M)

08m

gkg

(meanplusmnSE

M)

Liver

GPT

ALT

(52plusmn346

)UL

(72plusmn470)U

L01gt119875gt005

(86plusmn50)

UL

005gt119875gt002

(52plusmn348)U

L(48ndash80)U

L[19

]

GOTAST

(65plusmn657)U

L(157plusmn2424)

UL

01gt119875gt005

(251plusmn182)U

L001gt119875gt0001

(67plusmn321)U

L(14

ndash113)U

L[19

]

Kidn

eys

Urea

(28plusmn17

3)mgdL

(42plusmn308)m

gdL

005gt119875gt002

(576plusmn384)m

gdL

002gt119875gt001

(28plusmn033)m

gdL

(10ndash

28)m

gdL

[26]

Creatin

ine

(10plusmn0313)

mgdL

(174plusmn003)m

gdL

001gt119875gt0001

(21plusmn010)m

gdL

002gt119875gt001

(1plusmn006)m

gdL

(05ndash25)m

gdL

[26]

Heart

CK-M

B(132plusmn20)

UL

(21plusmn

15)U

L005gt119875gt002

(77plusmn1122)

UL

005gt119875gt002

(13plusmn056)U

L(lt25)U

Llowast

[2021]

LDH

(714plusmn318)U

L(206

4plusmn1598)

UL

119875lt0001

(2562plusmn2514

)UL

119875≪0001

(720plusmn470)U

L(559ndash2077)

UL

[46]

lowastCK

-MBactiv

ityislessthan

2in

healthyrabbitshow

everitisu

sually10ndash30

oftotalC

Kactiv

ity


0

50

100

150

200

250

300Se

rum

leve

l of G

PTG

OT

(UL

)

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

LRh

azya

stric

ta D

ecne

Rubi

a co

rdifo

lia L

Sa

pind

us m

ukor

ossi

Gae

rtn

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C) W

ight

and

Arn

Trich

odes

ma

indi

cum

(L)

SmZi

ngib

er o

fficin

ale R

osco

eRe

fere

nce s

tand

ard

anti

dote

GPT levelGOT level





3 Results







UL(mean plusmn SEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment














0051685 plusmn 757 05 gt 119875 gt 01






005














compare



4 Discussion






119875 valuecomment


119875 valuecomment
































compare







2is also found





UL (mean plusmnSEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment








































0

10

20

30

40

50

60

70Se

rum

leve

l of u

rea a

nd cr

eatin

ine (

mg

dL)

UreaCreatinine

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

L

Rhaz

ya st

ricta

Dec

neRu

bia

cord

ifolia

L

Sapi

ndus

muk

oros

si G

aert

nSt

enol

obiu

m st

ans (

L) S

eem

Term

inal

ia a

rjuna

(Rox

b ex

DC

) Wig

ht an

d A

rnTr

ichod

esm

a in

dicu

m (L

) Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te













1000

0

2000CK

-MB

(UL

)S

erum

leve

l of L

DH

LDHCK-MB

0-Al

bizi

a leb

beck

(L)

Bent

hAl

lium

cepa

L

Alliu

m sa

tivum

L

Alth

aea

officin

alis

LBa

uhin

ia va

riega

ta L

Br

assic

a ni

gra

(L)

W D

J K

och

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Cedr

us d

eoda

ra (R

oxb

ex D

Don

) G D

onCi

trus l

imon

(L)

Burm

f

Citru

llus c

oloc

ynth

is (L

) Sc

hrad

Cum

inum

cym

inum

L

Enico

stem

ma

hysso

pifo

lium

(Will

d) I

Ver

dFa

goni

a cr

etica

L

Leuc

as ca

pita

ta D

esf

Mat

thio

la in

cana

(L)

W T

Aito

nM

omor

dica

char

antia

L

Neriu

m in

dicu

m M

illO

cimum

sanc

tum

L

Pinu

s rox

burg

hii S

arg

Pista

cia in

tege

rrim

a J

L S

tew

art

Psor

alea

cory

lifol

ia L

Rhaz

ya st

ricta

Dec

ne

Rubi

a co

rdifo

lia L

Sapi

ndus

muk

oros

si G

aert

n

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C)

Trich

odes

ma

indi

cum

(L)

Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te


Wig

ht an

d A

rn





Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology



eforea

ndaft

ersnakev

enom

administratio

nin

different

experim

entalgroup

sofrabbits

Toxicitydeterm

ined

Markersof

snake

veno

mtoxicity

Group

Ibaseline

measurements

(meanplusmnSE

M)

Group

IIandIIIv

enom

injection

Group

IVnegativ

econ

trol

(meanplusmnSE

M)

Normalreference

values

repo

rted

References

04m

gkg

(meanplusmnSE

M)

08m

gkg

(meanplusmnSE

M)

Liver

GPT

ALT

(52plusmn346

)UL

(72plusmn470)U

L01gt119875gt005

(86plusmn50)

UL

005gt119875gt002

(52plusmn348)U

L(48ndash80)U

L[19

]

GOTAST

(65plusmn657)U

L(157plusmn2424)

UL

01gt119875gt005

(251plusmn182)U

L001gt119875gt0001

(67plusmn321)U

L(14

ndash113)U

L[19

]

Kidn

eys

Urea

(28plusmn17

3)mgdL

(42plusmn308)m

gdL

005gt119875gt002

(576plusmn384)m

gdL

002gt119875gt001

(28plusmn033)m

gdL

(10ndash

28)m

gdL

[26]

Creatin

ine

(10plusmn0313)

mgdL

(174plusmn003)m

gdL

001gt119875gt0001

(21plusmn010)m

gdL

002gt119875gt001

(1plusmn006)m

gdL

(05ndash25)m

gdL

[26]

Heart

CK-M

B(132plusmn20)

UL

(21plusmn

15)U

L005gt119875gt002

(77plusmn1122)

UL

005gt119875gt002

(13plusmn056)U

L(lt25)U

Llowast

[2021]

LDH

(714plusmn318)U

L(206

4plusmn1598)

UL

119875lt0001

(2562plusmn2514

)UL

119875≪0001

(720plusmn470)U

L(559ndash2077)

UL

[46]

lowastCK

-MBactiv

ityislessthan

2in

healthyrabbitshow

everitisu

sually10ndash30

oftotalC

Kactiv

ity


0

50

100

150

200

250

300Se

rum

leve

l of G

PTG

OT

(UL

)

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

LRh

azya

stric

ta D

ecne

Rubi

a co

rdifo

lia L

Sa

pind

us m

ukor

ossi

Gae

rtn

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C) W

ight

and

Arn

Trich

odes

ma

indi

cum

(L)

SmZi

ngib

er o

fficin

ale R

osco

eRe

fere

nce s

tand

ard

anti

dote

GPT levelGOT level





3 Results







UL(mean plusmn SEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment














0051685 plusmn 757 05 gt 119875 gt 01






005














compare



4 Discussion






119875 valuecomment


119875 valuecomment
































compare







2is also found





UL (mean plusmnSEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment








































0

10

20

30

40

50

60

70Se

rum

leve

l of u

rea a

nd cr

eatin

ine (

mg

dL)

UreaCreatinine

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

L

Rhaz

ya st

ricta

Dec

neRu

bia

cord

ifolia

L

Sapi

ndus

muk

oros

si G

aert

nSt

enol

obiu

m st

ans (

L) S

eem

Term

inal

ia a

rjuna

(Rox

b ex

DC

) Wig

ht an

d A

rnTr

ichod

esm

a in

dicu

m (L

) Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te













1000

0

2000CK

-MB

(UL

)S

erum

leve

l of L

DH

LDHCK-MB

0-Al

bizi

a leb

beck

(L)

Bent

hAl

lium

cepa

L

Alliu

m sa

tivum

L

Alth

aea

officin

alis

LBa

uhin

ia va

riega

ta L

Br

assic

a ni

gra

(L)

W D

J K

och

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Cedr

us d

eoda

ra (R

oxb

ex D

Don

) G D

onCi

trus l

imon

(L)

Burm

f

Citru

llus c

oloc

ynth

is (L

) Sc

hrad

Cum

inum

cym

inum

L

Enico

stem

ma

hysso

pifo

lium

(Will

d) I

Ver

dFa

goni

a cr

etica

L

Leuc

as ca

pita

ta D

esf

Mat

thio

la in

cana

(L)

W T

Aito

nM

omor

dica

char

antia

L

Neriu

m in

dicu

m M

illO

cimum

sanc

tum

L

Pinu

s rox

burg

hii S

arg

Pista

cia in

tege

rrim

a J

L S

tew

art

Psor

alea

cory

lifol

ia L

Rhaz

ya st

ricta

Dec

ne

Rubi

a co

rdifo

lia L

Sapi

ndus

muk

oros

si G

aert

n

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C)

Trich

odes

ma

indi

cum

(L)

Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te


Wig

ht an

d A

rn





Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


0

50

100

150

200

250

300Se

rum

leve

l of G

PTG

OT

(UL

)

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

LRh

azya

stric

ta D

ecne

Rubi

a co

rdifo

lia L

Sa

pind

us m

ukor

ossi

Gae

rtn

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C) W

ight

and

Arn

Trich

odes

ma

indi

cum

(L)

SmZi

ngib

er o

fficin

ale R

osco

eRe

fere

nce s

tand

ard

anti

dote

GPT levelGOT level





3 Results







UL(mean plusmn SEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment














0051685 plusmn 757 05 gt 119875 gt 01






005














compare



4 Discussion






119875 valuecomment


119875 valuecomment
































compare







2is also found





UL (mean plusmnSEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment








































0

10

20

30

40

50

60

70Se

rum

leve

l of u

rea a

nd cr

eatin

ine (

mg

dL)

UreaCreatinine

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

hCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCa

lotro

pis p

roce

ra (A

iton)

W T

Aito

nCe

drus

deo

dara

(Rox

b ex

D D

on) G

Don

Citru

s lim

on (L

) Bu

rm f

Ci

trullu

s col

ocyn

this

(L)

Schr

adCu

min

um cy

min

um L

En

icoste

mm

a hy

ssopi

foliu

m (W

illd

) I V

erd

Fago

nia

cret

ica L

Le

ucas

capi

tata

Des

fM

atth

iola

inca

na (L

) W

T A

iton

Mom

ordi

ca ch

aran

tia L

Ne

rium

indi

cum

Mill

Ocim

um sa

nctu

m L

Pi

nus r

oxbu

rghi

i Sar

gPi

stacia

inte

gerr

ima

J L

Ste

war

tPs

oral

ea co

rylif

olia

L

Rhaz

ya st

ricta

Dec

neRu

bia

cord

ifolia

L

Sapi

ndus

muk

oros

si G

aert

nSt

enol

obiu

m st

ans (

L) S

eem

Term

inal

ia a

rjuna

(Rox

b ex

DC

) Wig

ht an

d A

rnTr

ichod

esm

a in

dicu

m (L

) Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te













1000

0

2000CK

-MB

(UL

)S

erum

leve

l of L

DH

LDHCK-MB

0-Al

bizi

a leb

beck

(L)

Bent

hAl

lium

cepa

L

Alliu

m sa

tivum

L

Alth

aea

officin

alis

LBa

uhin

ia va

riega

ta L

Br

assic

a ni

gra

(L)

W D

J K

och

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Calo

tropi

s pro

cera

(Aito

n) W

T A

iton

Cedr

us d

eoda

ra (R

oxb

ex D

Don

) G D

onCi

trus l

imon

(L)

Burm

f

Citru

llus c

oloc

ynth

is (L

) Sc

hrad

Cum

inum

cym

inum

L

Enico

stem

ma

hysso

pifo

lium

(Will

d) I

Ver

dFa

goni

a cr

etica

L

Leuc

as ca

pita

ta D

esf

Mat

thio

la in

cana

(L)

W T

Aito

nM

omor

dica

char

antia

L

Neriu

m in

dicu

m M

illO

cimum

sanc

tum

L

Pinu

s rox

burg

hii S

arg

Pista

cia in

tege

rrim

a J

L S

tew

art

Psor

alea

cory

lifol

ia L

Rhaz

ya st

ricta

Dec

ne

Rubi

a co

rdifo

lia L

Sapi

ndus

muk

oros

si G

aert

n

Sten

olob

ium

stan

s (L

) See

mTe

rmin

alia

arju

na (R

oxb

ex D

C)

Trich

odes

ma

indi

cum

(L)

Sm

Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te


Wig

ht an

d A

rn





Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology




UL(mean plusmn SEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment














0051685 plusmn 757 05 gt 119875 gt 01






005














compare



4 Discussion






119875 valuecomment


119875 valuecomment
































compare







2is also found





UL (mean plusmnSEM)

119875 valuecomment

UL(mean plusmn SEM)

119875 valuecomment








































0

10

20

30

40

50

60

70Se

rum

leve

l of u

rea a

nd cr

eatin

ine (

mg

dL)

UreaCreatinine

Albi

zia

lebbe

ck (L

) Be

nth

Alliu

m ce

pa L

Al

lium

sativ

um L

Al

thae

a offi

cinal

is L

Bauh

inia

varie

gata

L

Bras

sica

nigr

a (L

) W

D J

Koc

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Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

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Volume 2014




Enzyme Research



Microbiology





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Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology




UL (mean plusmnSEM)

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ndar

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te


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ht an

d A

rn





Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


0

10

20

30

40

50

60

70Se

rum

leve

l of u

rea a

nd cr

eatin

ine (

mg

dL)

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Refe

renc

e sta

ndar

d an

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te


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ht an

d A

rn





Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology


1000

0

2000CK

-MB

(UL

)S

erum

leve

l of L

DH

LDHCK-MB

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bizi

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beck

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ra (R

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ex D

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onCi

trus l

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f

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llus c

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hrad

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lium

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ex D

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odes

ma

indi

cum

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Zing

iber

offi

cinal

e Ros

coe

Refe

renc

e sta

ndar

d an

ti do

te


Wig

ht an

d A

rn





Acknowledgments


References











2isozymesrdquo




















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology















































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology












Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology








Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

Documents

Research Article Naja naja karachiensis …downloads.hindawi.com/journals/bmri/2014/970540.pdfNaja naja karachiensis Envenomation: Biochemical Parameters for Cardiac, Liver, and Renal