Phytochemicals Mediated Remediation of Neurotoxicity Induced by

Review ArticlePhytochemicals Mediated Remediation of NeurotoxicityInduced by Heavy Metals

Vivek Kumar Gupta1 Shweta Singh1 Anju Agrawal2

Nikhat Jamal Siddiqi3 and Bechan Sharma1

1Department of Biochemistry University of Allahabad Allahabad 211002 India2Department of Zoology SNBVPG College CSJM University Kanpur 208001 India3Department of Biochemistry College of Science PO Box 22452 King Saud University Riyadh 11495 Saudi Arabia

Correspondence should be addressed to Bechan Sharma sharmabiyahoocom

Received 31 July 2015 Accepted 15 October 2015

Academic Editor Rona Ruth Ramsay

Copyright copy 2015 Vivek Kumar Gupta et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Almost all the environmental components including both the abiotic and biotic factors have been consistently threatened byexcessive contamination of heavy metals continuously released from various sources Different heavy metals have been reportedto generate adverse effects in many ways Heavy metals induced neurotoxicity and impairment in signalling cascade leading to celldeath (apoptosis) has been indicated by several workers On one hand these metals are required by the cellular systems to regulatevarious biological functions of normal cells while on the other their biomagnification in the cellular systems produces adverseeffects The mechanism by which the heavy metals induce neurotoxicity follows free radicals production pathway(s) specially thegeneration of reactive oxygen species and reactive nitrogen species These free radicals produced in excess have been shown tocreate an imbalance between the oxidative and antioxidative systems leading to emergence of oxidative stress which may causenecrosis DNA damage and many neurodegenerative disorders This mini review summarizes the current knowledge available onthe protective role of varied natural products isolated from different herbsplants in imparting protection against heavy metals(cadmium lead arsenic and mercury) mediated neurotoxicity

1 Introduction

The heavy metals are generally characterized as the inor-ganic elements having specific gravity five times of waterrsquosspecific gravity Among many heavy metals listed into the d-orbital elements of modern periodic table arsenic cadmiummercury and lead have got prime importance because oftheir pathophysiological significance as their bioaccumula-tion in living systems may cause severe damage to the vitalorgans namely nervous system and reproductive systemsgastrointestinal tract and mucous tissues Though the exactmechanism of their pathogenicity is not known but there arereports fromvarious laboratories indicating that the exposureof these heavy metals or their excess accumulation in thebody tissues may induce production of free radicals particu-larly the reactive oxygen species (ROS) and reactive nitrogenspecies (RNS) which finally culminate into production of

oxidative stress [1 2] Free radicals have been implicated intoDNA damage oxidation of thiol group(s) of proteins andlipid peroxidation [3] which is associated to onset of variousdiseases

Heavy metals reach into the environment from varioussources such as from the crust of Earth mining and groundwater commercial products industrial effluents industrialwastes vehicle emissions lead-acid batteries fertilizerspaints treated woods plastics floating on the worldrsquos oceansand aging water supply infrastructure folk remedies andcontaminated foods [2] Thus heavy metals contaminate andintoxicate soil water and food items (agricultural and animalproducts)These elementsmay enter human systems throughbreathing food or drink intake and contacts and so forthUpon accumulation they induce various adverse effectsin the body systems characterized as heavy metals medi-ated toxicity The present article is an endeavour to report

Hindawi Publishing CorporationBiochemistry Research InternationalVolume 2015 Article ID 534769 9 pageshttpdxdoiorg1011552015534769

2 Biochemistry Research International

Acetylcholinesteraseneuromuscular junctionspreganglionic neurons of thesympathetic nervous systembasal forebrain and brainstem complexes the receptorfor the merocrine sweat glands

5-HT (serotonin or 5-ydroxytryptamine (5-HT)ATP CGRP (calcitonin gene related peptide)dopamine GABA (120574-aminobutyric acid) GnRH (gonadotropin-releasing hormone)no (nitric oxide or nitrogenoxide or nitrogen monoxide) NPY (neuropeptide Y)VIP (vasoactive intestinal peptide)GnRH and substance P

Cholinergic system

Non-cholinergic system

Alzheimerrsquos and Parkinsonrsquos diseases

Mercury arseniccadmium and lead

Heavy metals

Figure 1 Effect of heavy metals on the cholinergic and noncholinergic systems associated to Alzheimerrsquos and Parkinsonrsquos diseases

the current account of phytochemicals mediated protectionfrom neurotoxicity induced by certain heavy metals in ani-mals including humans

2 Heavy Metals Influencing Cholinergic andNoncholinergic Systems

Heavy metals are shown to adversely influence the functionsof cholinergic and noncholinergic systemsThe association ofsuch impact of heavy metals with generation of Alzheimerrsquosand Parkinsonrsquos diseases has been documented A cholinergicsystem the most significant modulators of neurotransmis-sion systems in the brain regulates physiological and cogni-tive functions such as memory learning neuronal develop-ment and differentiation [4 5] Any substance or ligands hav-ing ability to produce alter or release acetylcholine or mimicits functions at the specific acetylcholine receptor type is cat-egorized as a cholinergic Similarly any receptor or synapseusing acetylcholine as a neurotransmitter is cholinergicThe parasympathetic nervous system or the preganglionicneurons of the sympathetic nervous system neuromuscularjunctions the basal forebrain brain stem and the receptorfor the merocrine sweat glands are also cholinergic sinceacetylcholine is involved in their functions On the otherhand the noncholinergic system involving a nonnoradrener-gic noncholinergic neurotransmitter (NANC) belongs to theautonomic nervous system (ANS) and includes serotonin or5-hydroxytryptamine (5-HT) ATP Calcitonin gene relatedpeptide (CGRP) Dopamine 120574-aminobutyric acid (GABA)Gonadotropin-releasing hormone (GnRH) nitric oxide ornitrogen oxide or nitrogen monoxide (NO) NeuropeptideY (NPY) Vasoactive intestinal peptide (VIP) and substanceP The heavy metals may form complexes with these cel-lular factors containing oxygen nitrogen or sulphur and

the resultant chemical species may produce toxicity whichmight lead to themodification in proteinrsquos structure or changein enzyme system cellular dysfunction and finally death ofthe cell The effects of heavy metals on the cholinergic andnoncholinergic systems are summarized in Figure 1

21 Mercury (Hg) All the natural forms of mercury (physicaland chemical forms) can produce toxic effect at high dosesThere are so many different forms of mercury which includesinorganic mercurous (Hg II) elemental mercury vapour(Hg) mercuric (Hg III) and organic mercuric compounds[33] which have toxic effects in organs like brain lungsand kidney [34] Natural mercury is present in liquid formwhen its oxidation state is zero It is categorized in transitionmetal element inmodern periodic table and is highly reactiveand toxic The chemistry of mercury its chemical typestheir metabolic transformations in different organs variedtoxic effects in mammalian systems and possible reactionmechanisms have been recently reviewed by Sharma et al(2014) [2] The toxicity of mercury is known to be mediatedby its binding with the thiol group of cellular proteins andenzymes which disrupts the cellular physiology in brainand other organs The pathophysiology of mercury toxicityrelates with the exposure of an individual by all the threeforms (solid liquid and gas) of this heavy metal Elemen-tal mercury crosses the blood brain barrier (BBB) readilywhere it concentrates in neuronal dense bodies of lysosomesand finally leads to neurotoxicity The symptoms of mer-cury toxicity include gastrointestinal disorders headachememory loss depression hypertension and neuromuscularpains in both adults and children The therapy of mer-cury poisoning has been advised to be done with differ-ent compounds including 23-dimercapto-1-propanesulfonicacid (DMPS) D-penicillamine (DPCN) dimercaprol (BAL)

Biochemistry Research International 3

Table 1 Phytochemicals as antidotes to heavy metals induced toxicity

Phytochemicals Sources Protective functions References

Allicin Garlic Reduces arsenic induced oxidative and arsenic toxicityby complex formation [6 7]

Anthocyaninflavonoids Cherry grapes andberries

Anthocyanin protects against Cd-induced oxidativestressAnthocyanin appears to effectively diminish Pbinduced oxidative stress

[8 9]

Catechins Tea cocoa peachand berries

Catechin inhibits Cd absorption and normalises bonemetabolic disorders through the bone mineral densitybone mineral content and bone calcium contentCatechin protects hepatic cell membrane fluidityincreases cell viability and modulates oxidative stress

[10 11]

Curcumin Turmeric

Curcumin protects against Cd-induced lipidperoxidationCurcumin binds Pb to form an excretable complexreducing neurotoxicity and nephrotoxicity

[12ndash15]

Naringenin Orange grapefruitand tomato

Naringenin quenches free radicals recoversantioxidant enzyme activity and chelates Cd [16]

120574-Oryzanol Rice120574-Oryzanol reduces the testicular Cd concentrationimproves 120575-aminolevulinic acid dehydratase (ALAD)activity and prevents lipid peroxidation

[17]

Quercetin

Onion tomato andradish olive oil redwine tea and so

forth

Induces the expression of endothelial nitric oxidesynthase (eNOS) inducible nitric oxide synthase(iNOS) and cyclooxygenase-2 (COX-2) Quercetinmodulates the mitogen-activated protein kinases(MAPKs) and nuclear factor kappa B (NF-120581B)signalling pathway and forms excretable complex withPb hydroxyl and superoxide groups scavenge radicalswhereas the phenolic groups act as possible chelatingsites

[18ndash23]

Phenolics Coriander fruitsvegetables and tea Act as antioxidants [13 24 25]

PhycocyanobilinCyanobacteria(Spirulina andChlorella)

Probably acting as antioxidants [26 27]

Puerarin Pueraria mirificaplant

Puerarin modulates the phosphoinositide-3-kinase(PI3K)protein kinase B (Akt)endothelial nitric oxidesynthase (eNOS) pathway reduces reactive oxygenspecies and protects against DNA damage andapoptosis

[22 28]

Vitamins A (120573-carotenes) B1 B6 Cand E

Nigella sativa Act as antioxidants [29ndash32]

and antioxidants such as N-acetylcysteine (NAC) and glu-tathione The treatment of mercury intoxication is mainlymanaged by chelation therapy for a long period of timeHowever some plant based principles have also been foundto exhibit immense potential to either protect or recoverfrom mercury induced toxicity in humans and animals Theameliorativeprotective properties of some phytochemicalshave been explained in a different section and Table 1

22 Cadmium (Cd) Cadmium as an important member ofthe last d-orbital group in modern periodic table has similarchemical properties respectively with zinc and mercurypreferably containing oxidation state +2 and low melting

point Cadmium poisoning takes place due to exposurethrough inhalation of cadmium fumes in the atmospheresand intake of food water and tobacco Exposure to cadmiumleads to occurrence of several ailments such as anaemiaosteoporosis blood brain and skin related diseases Expo-sure to Cd is reported to cause malfunctioning of fetus whichincludes ablephary club foot exencephaly micrognathiaand microphthalmia Severe exposure to calcium may harmboth the fetus and the mother by enhancing the numbersof micronucleated polychromatic erythrocytes (MNPE) andmicronucleated normochromatic erythrocytes (MNNE) [35]Cadmium is known to produce free radicals and oxidativestress which is one of the mechanisms of its toxicity [36] as


it combines with thiol groups of enzymes involved in antiox-idant mechanisms and inactivates them Since Cadmiumcan replace magnesium and calcium in certain biologicalsystems [37] it adversely influences the concerned biologicalprocesses Cadmium exposure may also alter DNA repairactivity [38] Cadmium intoxicated individual may sufferfrom neurotoxicity and respiratory circulatory excretoryand gastrointestinal disorders Chronic exposure of cadmiumresults into appearance of certain clinical symptoms suchas headache sleep disorders and memory deficits increasedsalivation throat choking and renal and hepatic failureswhich are associated to the alterations in metabolism of neu-rotransmitters particularly of GABA and serotonin Similarto mercury the treatment of cadmium poisoning involvesapplication of antioxidants chelators [2] and phytochemicalsas described in a separate section as well as in Table 1

23 Arsenic (As) Arsenic exists in trivalent arsenite (As III)and pentavalent (As V) arsenate forms Arsenic accumulatesin the body through seafood inhalation and absorptionthrough skin and causes disorders in GI tract neurotrans-mission blood circulation system and respiratory systemArsenic exposure is known to produce free radicals and hencegenerates oxidative stress It adversely influences the activitiesand levels of antioxidative elements such as superoxide dis-mutase (SOD) catalase (CAT) glutathione peroxidase (GPx)heme oxygenase-1 (HO-1) and the nonenzymatic factorssuch as sulfhydryl group containing peptides and proteinsin human systems Arsenic toxicity adversely influencesKrebs cycle and oxidative phosphorylation leading to thedepletion of energy as well as rapid depletion of thiol groupcontaining critical peptidesproteins [39] Arsenic poisoningis characterized by burning and numbness in the hands andfeet and alterations in functions of neurotransmission andcardiovascular systems In particular in the patients withdiabetes mellitus arsenic toxicity may be considered as amajor contributor to vascular and neurological complications[40 41] Normal value for urine is less than 50mgL andwhole blood arsenic level is usually less than 1mgdL [39]The treatment of arsenic intoxication is carried out mainlyby chelation therapy using dimercaprol or succimer (23-dimercaptosuccinic acid DMSA) and aqueous garlic extract[42] However some phytochemicals have been found tobe very useful in combating arsenic toxicity as displayed inTable 1 and in the following section

24 Lead (Pb) Lead being used in batteries metal productsand medical appliances has been found to be an importantcause of concern of heavymetal toxicity in biological systemsexposed to it [43] According to the Centres for DiseaseControl and Prevention (CDC)-USA a blood lead level(BLL) of 10 120583gdL or above is a cause for concern Leadmediated toxicity includes varied physiological biochemicaland behavioural dysfunctions in humanrsquos peripheral andcentral nervous systems blood circulatory cardiovascularexcretory metabolic and reproductive systems [44] It causesneurotoxicity in general but significantly reduces paediatriccognitive functions [45] The prime mechanism of lead

mediated neurotoxicity is associated with the production ofexcess free radical species and oxidative stress which haspotential to cause perturbations in the brain [1 46 47] SinceLead efficiently crosses the BBB [48] and it easily substitutescalcium ions interferes with the regulatory action of calciumon brain cells and disrupts its intracellular activities [48] thepathogenic symptoms of lead toxicity include hypertensioncognitive deficit [49] anaemia peripheral motor neuropathyand gastrointestinal disorders The chronic lead toxicity(gt70mgdL) in children may lead to frequent occurrenceof coma seizures and altered mental status The effectivetreatment of lead toxicity includes using preventivemeasureschelation therapy and application of some herbal prepara-tions (Table 1)

3 Phytochemicals Used in Amelioration ofHeavy Metals Induced Neurotoxicity

Despite the fact that the phytochemicals contain plenty offlavonoids and polyphenols like antioxidants they may alsohelp ameliorate the heavy metals mediated toxicity in humanand other animals The oral administration of Arthrospiramaxima (Spirulina) has been shown to significantly reducecadmium mediated genotoxic effects which has been cor-roborated to some extent with the antioxidant potential ofthe aforesaid algae [35] Very recently cadmium inducedarterial and cardiac injuries could be significantly reducedby introducing dietary soybean supplementation in diet [48]Mohammed et al (2014) [49] have indicated that Nigellasativa seed oil contains strong antioxidant properties andhencemay protect vital organs (brain and kidney) of the bodyfrom oxidative damages They have proposed that Nigellasativa seed oil and the virgin olive oils can be used by manyworkers employed in cement factories wherein Cd is sofrequently liberated in the environment The phytochemicalssuch as vitamin C vitamin E phycocyanobilin and carotenesare presented into some cyanobacterial species such asSpirulina and Chlorella which have been found to impartprotection to rats exposed to lead and cadmium [26 27 3031]

The application of vitamin E has demonstrated that itsadministration along with cadmium caused notable reduc-tion in accumulation of this metal in different key tissues(kidney liver and blood) of the body [50 51] Similar tothe antioxidative role of fat soluble vitamin E the watersoluble vitamins (C B1 and B6) have been found to protectthe organs of rats from cadmium and lead toxicities [2932] When vitamins C and E were administered together incadmium intoxicated rats the level of oxidative stress wassharply reduced [52 53] In one of the similar experimentswhen vitamin E was supplemented to Pb treated erythro-cytes the activity of 120575-aminolevulinic dehydratase and lipidoxidation was significantly reduced [54] 120573-Carotene a red-orange pigment fat soluble organic compound abundant inplants and fruits has been found to serve as a precursorof vitamin A (retinol) It has been reported to be asso-ciated with increased rate of lung cancer among smokers[55]


Using garlic extract some workers were able to demon-strate reduction in cadmium and lead mediated mitochon-drial injury and apoptosis in tissue culture models as wellas neural hepatic renal and haematic damage in rats [56ndash58] Garlic is shown to possess higher antioxidant potentialthan onion [59] whichmay be associated with the presence ofallicin [7] Aslani et al (2010) [6] have shown that the admin-istration of the mixture of garlic extract and dimercaptosuc-cinic acid (DMSA) may be able to very effectively amelioratethe rats suffering from lead poisoning In addition to manyhealth benefits garlic also acts as a booster of immunity andcontains antiaging substance(s) [60]The extract of garlic hasbeen reported to act as a potential antidote to the toxic effectsof sodium arsenite [61 62] It is thought that the protectiveeffect of garlic from arsenic toxicity is rendered through thethiosulfur components present in the extract which would bemaking some stable chemical complexes after reacting witharsenic chemical species and inactivating arsenic mediatedtoxicity [19] The existing information suggests that presenceof various components in the aqueous extracts of garlic ingeneral and allicin in particular may participate in chelationof arsenic [63 64] The reduction in the toxicity inducedby arsenic has been achieved by the coadministration ofplant extracts such as Allium sativum Aloe vera barbadensisCentella asiatica curcumin and Hippophae rhamnoides asrecorded by evaluating hematological renal and hepaticparameters in experimental animals [19 65ndash69] In order tomitigate the toxicity of arsenic not many plants have beenexplored to be used as a medicine

However the leaf extracts of Annona muricata havebeen found to have potential to significantly reduce arsenicmediated neurotoxicity [70ndash72] The methanolic extract ofthe leaves of A muricata was found to exhibit higher activitythan the aqueous extract They observed a dose-dependentdecrease in arsenic toxicityThese authors have also indicatedthat tea extract could also be useful in arsenic poisoningcases to reduce the toxicity H rhamnoides is a rich sourceof vitamins A C and E carotenoids and organic acids whichgives positive effects on arsenic induced toxicity have beenattributed to the presence of high content of antioxidantsubstances [67 69]

The quercetin (3101584034101584057-pentahydroxyflavone) a die-tary flavonoid is found in fruits and vegetables olive oilred wine and tea [18 19] It has been observed to containfree radical quenching activity which scavenges free radicals(Hertog et al 1995) [18] induced by arsenic exposure whenadministered either alone or in combination with a thiolchelator [73 74] It has been observed that a nanocapsu-lated drug delivery system of Quercetin can provide bettermedication to prevent arsenic induced damage than bulkadministration of Quercetin [73 75] The extracts froma few other traditional medicinal plants such as Moringaoleifera A barbadensis and C asiatica have also been foundto offer beneficial effects by protecting the vital organs ofthe body probably by reducing oxidative stress [66 68 76]and depletion of arsenic concentration in tissue [68] andthrough the interactions of phytochemicals with cysteine-and methionine-rich proteins [73 76 77]

Tomato extract has been shown to reduce bioaccumu-lation of heavy metals [78] and acts as a strong antiox-idant and protectant from cadmium and lead mediatedtoxicities in rats [79 80] This property of tomato maybe associated to the presence of certain metal chelatingproteins and phytochelatins [81] Some Indian spices suchas coriander is shown to contain phenolic acid com-pounds like caffeic acid chlorogenic acid vanillic acid p-coumaric acid ferulic acid (cis and trans form) [24 25]and curcumin 17-bis (4-hydroxy-3-methoxyphenyl)-16-heptadiene-35-Dione (diferuloyl methane) isolated fromturmeric has anti-inflammatory and antioxidant properties[82] which enables it to protect the cadmium exposed ratsfrom nephrotoxicity [13] During a field trial conducted inWest Bengal curcumin was derived from turmeric [12]

For a very long time the antioxidative properties of teahave been known [83ndash85] The catechins present in greentea and the flavonoids and phenols of curry leaves as wellas fruits (grapes) have been demonstrated to exhibit similarprotective effects [86 87] in the cases of lead and cadmiumpoisoning The major green tea polyphenols with antioxi-dant properties may include (minus)-epigallocatechin-3-gallate(EGCG) (minus)-epicatechin-3-gallate (ECG) (minus)-epigallocate-chin (EGC) (minus)-epicatechin (EC) (+)-gallocatechin (GC)and (+)-catechin [83 85]

Chinthana and Ananthi (2012) [88] have reported thatthe neurotoxicity induced by lead in albino mice could besignificantly reduced by oral administration of extract of Snigrum and S trilobatum leaves for 30 days They observedsubstantial increase in the activities of antioxidant enzymessuch as SOD CAT GPx and reduced lipid peroxidation Snigrum is a weed and some species of it may be toxic tohumans and animalsThis plant is widely used as a traditionalmedicine [89] Similar observations have been recorded byZaidi et al (2014) [90] when they evaluated the prophylacticor curative antioxidant efficacy of crude extract and the activeconstituent of S nigrum leaves in the brain of stressed rat

A summary of the key phytochemicals isolated fromdifferent plant sources and characterised for protectionfrom heavy metals mediated neurotoxicity are presented inTable 1 A graphical sketch of protection offered by dietarysupplements against the heavy metals induced alterationsin biochemical and physiological functions of the body isdisplayed in Figure 2

4 Conclusion

The heavy metals exhibit the ability to induce oxidative stressby generating ROS Oxidative stress due to heavy metalsis the outcome of a negative shift of the balance betweenthe production of ROS and the ability of the biologicalsystems to readily counteract the ROS mediated damageor repair of it rapidly The heavy metals toxicity is causedeither by their direct binding with thiol groups of the pro-teinsenzymes thereby causing perturbations in their three-dimensional conformations or by replacing the divalentmetal ions from their catalytic pocket which are essentiallyrequired by concerned proteinsenzymes as cofactors fortheir optimal activity In either of these situations these


Accumulation in tissue andbiomagnifications

Metabolic disorders of essential metals due to oxidative stress caused by heavy metals

Necrosis of celltissue andcell death

Dietary supplementsEssential metals vitamins and edibleplants having phytochemicals for counteraction of heavy metal toxicity

Heavy metal toxicityoral through inhalationopen exposure to skin

Recommended food Tomatoes berries onions garlic gingersgrapes and so forth

Figure 2 Impact of heavy metals on human system

biomolecules tend to lose their native characteristics dueto unfolding or denaturation and then their functions aregreatly compromised which lead to serious bearings on totheir biological activity and finally the cellular health Allforms of life maintain a reducing environment within theircells This reducing environment is preserved by enzymesthat maintain the reduced state through a constant input ofmetabolic energy Disturbances in this normal redox state byheavy metals can cause toxic effects indirectly through theproduction of peroxides and free radicals that induce oxida-tive stress which is responsible for the damage of several keycomponents of the cells including proteins lipid and DNAThe amelioration of neurotoxicity induced by certain heavymetals by herbal principles is of great significance as they arecost effective and highly active and lead to no side effectsIn addition to them the application of certain vitamins anda number of chelating organic molecules is being tried withthe expectation that they would make coordinate complexeswith these heavy metals and help remove them makingthe affected organs or tissues free from metalrsquos burden andtoxicity Although coadministration of antioxidants (naturalherbal or synthetic) or with other chelating agents has shownto improve removal of toxic metals from the system as wellas clinical recoveries in animal models still the in-depthclinical studies with preexisting or newer chelating agents arerequired to be done to reap real benefit with the least sideeffects In case of humans it is also important to find out thesuitable dose and duration of treatment to decide the optimaltherapeutic index for any of the drugs to be given in isolationor in different combinations In conclusion the present stageof knowledge about the impact of heavy metals in biologicalsystems indicates the enhanced formation of free radicals andROS or RNS or their intermediates causing neurotoxicity andother ailments and that could be efficiently managed by usingdifferent preparations fromanumber of traditionalmedicinalplants

Conflict of Interests

The authors report no declarations of interests

Acknowledgments

Vivek Kumar Gupta and Shweta Singh are grateful to theUniversity Grant Commission New Delhi for providingresearch fellowships for this work at the Department ofBiochemistry University of Allahabad India Nikhat JamalSiddiqi gratefully thanks the Research Center Female Centerfor Scientific and Medical Colleges King Saud UniversityRiyadh for the support

References

[1] S J S Flora S Chouhan G M Kannan M Mittal and HSwarnkar ldquoCombined administration of taurine and monoi-soamylDMSAprotects arsenic induced oxidative injury in ratsrdquoOxidative Medicine and Cellular Longevity vol 1 no 1 pp 39ndash45 2008

[2] B Sharma S Singh and N J Siddiqi ldquoBiomedical implicationsof heavy metals induced imbalances in redox systemsrdquo BioMedResearch International vol 2014 Article ID 640754 26 pages2014

[3] M Valko H Morris andM T D Cronin ldquoMetals toxicity andoxidative stressrdquoCurrentMedicinal Chemistry vol 12 no 10 pp1161ndash1208 2005

[4] A E Power ldquoMuscarinic cholinergic contribution to memoryconsolidation with attention to involvement of the basolateralamygdalardquo Current Medicinal Chemistry vol 11 no 8 pp 987ndash996 2004

[5] V Fodale D Quattrone C Trecroci V Caminiti and L B San-tamaria ldquoAlzheimerrsquos disease and anaesthesia implications forthe central cholinergic systemrdquo British Journal of Anaesthesiavol 97 no 4 pp 445ndash452 2006


[6] M R Aslani V Najarnezhad and M Mohri ldquoIndividualand combined effect of meso-23-dimercaptosuccinic acid andallicin on blood and tissue lead content inmicerdquo PlantaMedicavol 76 no 3 pp 241ndash244 2010

[7] D Shahsavani H Baghshani and E Alishahi ldquoEfficacy ofallicin in decreasing lead (Pb) accumulation in selected tissuesof lead-exposed common carp (Cyprinus carpio)rdquo BiologicalTrace Element Research vol 142 no 3 pp 572ndash580 2011

[8] E Kowalczyk A Kopff P Fijałkowski et al ldquoEffect of antho-cyanins on selected biochemical parameters in rats exposed tocadmiumrdquoActa Biochimica Polonica vol 50 no 2 pp 543ndash5482003

[9] A A El-Nekeety A A El-Kady M S Soliman N S Hassanand M A Abdel-Wahhab ldquoProtective effect of Aquilegia vul-garis (L) against lead acetate-induced oxidative stress in ratsrdquoFood and Chemical Toxicology vol 47 no 9 pp 2209ndash22152009

[10] L Chen X Yang H Jiao and B Zhao ldquoTea catechins protectagainst lead-induced cytotoxicity lipid peroxidation andmem-brane fluidity in HepG2 cellsrdquo Toxicological Sciences vol 69 no1 pp 149ndash156 2002

[11] J-H Choi I-K Rhee K-Y Park K-Y Park J-K Kim and S-JRhee ldquoAction of green tea catechin on bone metabolic disorderin chronic cadmium-poisoned ratsrdquo Life Sciences vol 73 no 12pp 1479ndash1489 2003

[12] J Biswas D Sinha S Mukherjee S Roy M Siddiqi and MRoy ldquoCurcumin protects DNA damage in a chronically arsenic-exposed population of West Bengalrdquo Human and ExperimentalToxicology vol 29 no 6 pp 513ndash524 2010

[13] P Singh V Sankhla P Mogra et al ldquoProtective effect ofcurcumin on cadmium-chloride induced nephrotoxicity inswiss albino micerdquo Journal of Herbal Medicine and Toxicologyvol 4 no 2 pp 215ndash219 2010

[14] S Daniel J L Limson A Dairam G M Watkins and S DayaldquoThrough metal binding curcumin protects against lead- andcadmium-induced lipid peroxidation in rat brain homogenatesand against lead-induced tissue damage in rat brainrdquo Journal ofInorganic Biochemistry vol 98 no 2 pp 266ndash275 2004

[15] V Eybl D Kotyzova and J Koutensky ldquoComparative studyof natural antioxidants-curcumin reservetrol andmelatonin-incadmium-induced oxidative damage in micerdquo Toxicology vol225 no 2-3 pp 150ndash156 2006

[16] J Renugadevi and S M Prabu ldquoNaringenin protects againstcadmium-induced oxidative renal dysfunction in ratsrdquo Toxicol-ogy vol 256 no 1-2 pp 128ndash134 2009

[17] C C Spiazzi V Manfredini F E Barcellos da Silva et al ldquo120574-Oryzanol protects against acute cadmium-induced oxidativedamage in mice testesrdquo Food and Chemical Toxicology vol 55pp 526ndash532 2013

[18] M G L Hertog D Kromhout C Aravanis et al ldquoFlavonoidintake and long-term risk of coronary heart disease and cancerin the SevenCountries StudyrdquoArchives of InternalMedicine vol155 no 4 pp 381ndash386 1995

[19] S J S Flora A Mehta and R Gupta ldquoPrevention of arsenic-induced hepatic apoptosis by concomitant administration ofgarlic extracts inmicerdquoChemico-Biological Interactions vol 177no 3 pp 227ndash233 2009

[20] W Banner Jr M Koch D M Capin S B Hopf S Changand T G Tong ldquoExperimental chelation therapy in chromiumlead and boron intoxication with N-acetylcysteine and othercompoundsrdquo Toxicology and Applied Pharmacology vol 83 no1 pp 142ndash147 1986

[21] A I Morales C Vicente-Sanchez M Jerkic et al ldquoEffectof quercetin on metallothionein nitric oxide synthases andcyclooxygenase-2 expression on experimental chronic cad-mium nephrotoxicity in ratsrdquo Toxicology and Applied Pharma-cology vol 210 no 1-2 pp 128ndash135 2006

[22] C-M Liu Y-Z Sun J-M Sun J-Q Ma and C ChengldquoProtective role of quercetin against lead-induced inflammatoryresponse in rat kidney through the ROS-mediated MAPKs andNF-120581B pathwayrdquo Biochimica et Biophysica Acta vol 1820 no 10pp 1693ndash1703 2012

[23] C-M Liu G H Zheng Q L Ming J M Sun and C ChengldquoProtective effect of quercetin on lead-induced oxidative stressand endoplasmic reticulum stress in rat liver via the IRE1JNKand PI3KAkt pathwayrdquo Free Radical Research vol 47 no 3 pp192ndash201 2013

[24] V S Nambiar M Daniel and P Guin ldquoCharacterizationof polyphenols from coriander leaves (Coriandrum sativum)red amaranthus (A paniculatus) and green amaranthus (Afrumentaceus) using paper chromatography and their healthimplicationsrdquo Journal of Herbal Medicine and Toxicology vol 4no 1 pp 173ndash177 2010

[25] U Rajeshwari and B Andallu ldquoMedicinal benefits of coriander(Coriandrum sativum L)rdquo Spatula DD vol 1 no 1 pp 51ndash582011

[26] J-Y Shim and A-S Om ldquoChlorella vulgaris has preventiveeffect on cadmium induced liver damage in ratsrdquo Molecular ampCellular Toxicology vol 4 pp 138ndash143 2008

[27] H Yun I Kim S-H Kwon J-S Kang and A-S Om ldquoProtec-tive effect of Chlorella vulgaris against Lead-Induced oxidativestress in rat brainsrdquo Journal of Health Science vol 57 no 3 pp245ndash254 2011

[28] J Jungsukcharoen B A Dhiani W Cherdshewasart NVinayavekhin P Sangvanich and C Boonchird ldquoPuerariamirifica leaves an alternative potential isoflavonoid sourcerdquoBioscience Biotechnology and Biochemistry vol 78 no 6 pp917ndash926 2014

[29] J A Simon and E S Hudes ldquoRelationship of ascorbic acidto blood lead levelsrdquo The Journal of the American MedicalAssociation vol 281 no 24 pp 2289ndash2293 1999

[30] A Amin A A Hamza S Daoud et al ldquoSpirulina protectsagainst cadmium-induced hepatotoxicity in ratsrdquo AmericanJournal of Pharmacology and Toxicology vol 1 no 2 pp 21ndash252006

[31] J-Y Shim H-S Shin J-G Han et al ldquoProtective effects ofChlorella vulgaris on liver toxicity in cadmium-administeredratsrdquo Journal of Medicinal Food vol 11 no 3 pp 479ndash485 2008

[32] G H El-Sokkary and E A Awadalla ldquoThe protective role ofvitamin C against cerebral and pulmonary damage induced bycadmium chloride in male adult albino ratrdquo Open Neuroen-docrinology Journal vol 4 pp 1ndash8 2011

[33] B Hultberg A Andersson and A Isaksson ldquoInteraction ofmetals and thiols in cell damage and glutathione distributionpotentiation of mercury toxicity by dithiothreitolrdquo Toxicologyvol 156 no 2-3 pp 93ndash100 2001

[34] W F Fitzgerald and T W Clarkson ldquoMercury and monometh-ylmercury present and future concernsrdquo Environmental HealthPerspectives vol 96 pp 159ndash166 1991

[35] N Arguelles-Velazquez I Alvarez-Gonzalez E Madrigal-Bujaidar and G Chamorro-Cevallos ldquoAmelioration of cad-mium-produced teratogenicity and genotoxicity in mice givenArthrospira maxima (Spirulina) treatmentrdquo Evidence-Based


Complementary and Alternative Medicine vol 2013 Article ID604535 8 pages 2013

[36] B Halliwell and JM C Gutteridge Free Radicals in Biology andMedicine Uarendon Press Oxford UK 2nd edition 1989

[37] S D Lane D R Cherek O V Tcheremissine LM Lieving andC J Pietras ldquoAcute marijuana effects on human risk takingrdquoNeuropsychopharmacology vol 30 no 4 pp 800ndash809 2005

[38] G Bertin and D Averbeck ldquoCadmium cellular effects mod-ifications of biomolecules modulation of DNA repair andgenotoxic consequences (a review)rdquo Biochimie vol 88 no 11pp 1549ndash1559 2006

[39] S A Stice ldquoSpeciation metabolism toxicity and protein-binding of different arsenic species in human cellsrdquo FIUElectronic Theses and Dissertations 1203 2014

[40] A Parthiban S Vijayalingam K R Shanmugasundaram andR Mohan ldquoOxidative stress and the development of diabeticcomplicationsmdashantioxidants and lipid peroxidation in erythro-cytes and cell membranerdquo Cell Biology International vol 19 no12 pp 987ndash993 1995

[41] K Yamanaka F Takabayashi M Mizoi et al ldquoOral exposure ofdimethyl arsenic acid a main metabolite of inorganic arsenicsin mice leads to an increase in 8-Oxo-21015840-deoxyguanosinelevel specially in the target organs for arsenic carcinogenesisrdquoBiochemical and Biophysical Research Communications vol 287pp 66ndash70 2001

[42] B Das S Mandal and K Chaudhuri ldquoRole of arginine acomponent of aqueous garlic extract in remediation of sodiumarsenite induced toxicity in A375 cellsrdquoToxicology Research vol3 no 3 pp 191ndash196 2014

[43] C Nava-Ruız and M Mendez-Armenta ldquoCadmium lead thal-lium occurrence neurotoxicity and histopathological changesof the nervous systemrdquo in Pollutant Diseases Remediation andRecycling vol 4 of Environmental Chemistry for a SustainableWorld pp 321ndash349 Springer 2013

[44] I Lancranjan H I Popescu O Gavanescu I Klepsch and MSerbanescu ldquoReproductive ability of workmen occupationallyexposed to leadrdquo Archives of Environmental Health vol 30 no8 pp 396ndash401 1975

[45] G Lockith ldquoBlood lead levels in childrenrdquo Canadian MedicalAssociation Journal vol 149 no 2 pp 139ndash142 1993

[46] S J Yiin andTH Lin ldquoLead-catalyzed peroxidation of essentialunsaturated fatty acidrdquo Biological Trace Element Research vol50 no 2 pp 167ndash172 1995

[47] B O Adegbesan and G A Adenuga ldquoEffect of lead expo-sure on liver lipid peroxidative and antioxidant defense sys-tems of protein-undernourished ratsrdquo Biological Trace ElementResearch vol 116 no 2 pp 219ndash225 2007

[48] R Brochin S Leone D Phillips et al ldquoThe cellular effect of leadpoisoning and its clinical picturerdquo Georgetown UndergraduateJournal of Health Sciences vol 5 pp 1ndash8 2008

[49] E Mohammed K Hashem andM Rheim ldquoBiochemical studyon the impact ofNigella sativa and virgin olive oils on cadmium-induced nephrotoxicity and neurotoxicity in ratsrdquo Journal ofInvestigational Biochemistry vol 3 no 2 pp 71ndash78 2014

[50] S K Tandon S Singh and M Dhawan ldquoPreventive effect ofvitamin E in cadmium intoxicationrdquo Biomedical and Environ-mental Sciences vol 5 no 1 pp 39ndash45 1992

[51] S Nemmiche D Chabane-Sari and P Guiraud ldquoRole of 120572-tocopherol in cadmium-induced oxidative stress in Wistar ratrsquosblood liver and brainrdquoChemico-Biological Interactions vol 170no 3 pp 221ndash230 2007

[52] R S Gupta E S Gupta B KDhakal A RThakur and J AhnnldquoVitamin C and vitamin E protect the rat testes from cadmium-induced reactive oxygen speciesrdquoMolecules andCells vol 17 no1 pp 132ndash139 2004

[53] U R Acharya M Mishra J Patro and M K Panda ldquoEffectof vitamins C and E on spermatogenesis in mice exposed tocadmiumrdquo Reproductive Toxicology vol 25 no 1 pp 84ndash882008

[54] A Rendon-Ramirez J Cerbon-Solorzano M Maldonado-Vega M A Quintanar-Escorza and J V Calderon-SalinasldquoVitamin-E reduces the oxidative damage on 120575-aminolevulinicdehydratase induced by lead intoxication in rat erythrocytesrdquoToxicology in Vitro vol 21 no 6 pp 1121ndash1126 2007

[55] F M El-Demerdash M I Yousef F S Kedwany and H HBaghdadi ldquoCadmium-induced changes in lipid peroxidationblood hematology biochemical parameters and semen qualityof male rats protective role of vitamin E and 120573-carotenerdquo Foodand Chemical Toxicology vol 42 no 10 pp 1563ndash1571 2004

[56] V Sharma A Sharma and L Kansal ldquoThe effect of oral admin-istration of Allium sativum extracts on lead nitrate inducedtoxicity in male micerdquo Food and Chemical Toxicology vol 48no 3 pp 928ndash936 2010

[57] A O Lawal and E M Ellis ldquoThe chemopreventive effects ofaged garlic extract against cadmium-induced toxicityrdquo Environ-mental Toxicology and Pharmacology vol 32 no 2 pp 266ndash2742011

[58] A Sadeghi A E Bideskan F Alipour A Fazel and H HaghirldquoThe effect of ascorbic acid and garlic administration on lead-induced neural damage in rat offspringrsquos hippocampusrdquo IranianJournal of BasicMedical Sciences vol 16 no 2 pp 157ndash164 2013

[59] N Benkeblia ldquoFree-radical scavenging capacity and antioxidantproperties of some selected onions (Allium cepa L) and garlic(Allium sativum L) extractsrdquo Brazilian Archives of Biology andTechnology vol 48 no 5 pp 753ndash759 2005

[60] K Rahman ldquoGarlic and aging new insights into an old remedyrdquoAgeing Research Reviews vol 2 no 1 pp 39ndash56 2003

[61] T Das A Roychoudhury A Sharma and G Talukder ldquoMod-ification of clastogenicity of three known clastogens by garlicextract in mice in vivordquo Environmental and Molecular Mutage-nesis vol 21 no 4 pp 383ndash388 1993

[62] A RoyChoudhury T Das A Sharma and G TalukderldquoDietary garlic extract in modifying clastogenic effects ofinorganic arsenic in mice two-generation studiesrdquo MutationResearchEnvironmental Mutagenesis and Related Subjects vol359 no 3 pp 165ndash170 1996

[63] H Amagase B L Petesch H Matsuura S Kasuga and YItakura ldquoIntake of garlic and its bioactive componentsrdquo Journalof Nutrition vol 131 no 3 2001

[64] R Chowdhury A Dutta S R Chaudhuri N Sharma A KGiri and K Chaudhuri ldquoIn vitro and in vivo reduction ofsodium arsenite induced toxicity by aqueous garlic extractrdquoFood and Chemical Toxicology vol 46 no 2 pp 740ndash751 2008

[65] H Tiwari and M V Rao ldquoCurcumin supplementation protectsfrom genotoxic effects of arsenic and fluoriderdquo Food andChemical Toxicology vol 48 no 5 pp 1234ndash1238 2010

[66] R Gupta and S J S Flora ldquoProtective value ofAloe vera againstsome toxic effects of arsenic in ratsrdquo Phytotherapy Research vol19 no 1 pp 23ndash28 2005

[67] R Gupta and S J S Flora ldquoTherapeutic value of Hippophaerhamnoides L against subchronic arsenic toxicity in micerdquoJournal of Medicinal Food vol 8 no 3 pp 353ndash361 2005


[68] R Gupta and S J S Flora ldquoEffect of Centella asiatica on arsenicinduced oxidative stress and metal distribution in ratsrdquo Journalof Applied Toxicology vol 26 no 3 pp 213ndash222 2006

[69] R Gupta and S J S Flora ldquoProtective effects of fruit extracts ofHippophae rhamnoides L against arsenic toxicity in Swiss albinomicerdquo Human and Experimental Toxicology vol 25 no 6 pp285ndash295 2006

[70] K Jomova Z Jenisova M Feszterova et al ldquoArsenic toxicityoxidative stress and human diseaserdquo Journal of Applied Toxicol-ogy vol 31 no 2 pp 95ndash107 2011

[71] K Sarkozi A Papp E Horvath et al ldquoGreen tea and vitaminC ameliorate some neuro-functional and biochemical signs ofarsenic toxicity in ratsrdquo Nutritional Neuroscience 2014

[72] V C George D R Kumar P K Suresh and R A KumarldquoIn vitro protective potentials of Annona muricata leaf extractsagainst sodium arsenite-induced toxicityrdquoCurrent DrugDiscov-ery Technologies vol 12 no 1 pp 59ndash63 2015

[73] D Mishra and S J S Flora ldquoQuercetin administration duringchelation therapy protects arsenic-induced oxidative stress inmicerdquo Biological Trace Element Research vol 122 no 2 pp 137ndash147 2008

[74] K Bhatt and S J S Flora ldquoOral co-administration of 120572-lipoicacid quercetin and captopril prevents gallium arsenide toxicityin ratsrdquo Environmental Toxicology and Pharmacology vol 28no 1 pp 140ndash146 2009

[75] A Ghosh A K Mandal S Sarkar S Panda and N DasldquoNanoencapsulation of quercetin enhances its dietary efficacyin combating arsenic-induced oxidative damage in liver andbrain of ratsrdquo Life Sciences vol 84 no 3-4 pp 75ndash80 2009

[76] R Gupta G M Kannan M Sharma and S J S FloraldquoTherapeutic effects of Moringa oleifera on arsenic-inducedtoxicity in ratsrdquo Environmental Toxicology and Pharmacologyvol 20 no 3 pp 456ndash464 2005

[77] R Gupta D K Dubey G M Kannan and S J S Flora ldquoCon-comitant administration ofMoringa oleifera seed powder in theremediation of arsenic-induced oxidative stress in mouserdquo CellBiology International vol 31 no 1 pp 44ndash56 2007

[78] C R Nwokocha M I Nwokocha I Aneto et al ldquoComparativeanalysis on the effect of Lycopersicon esculentum (tomato) inreducing cadmium mercury and lead accumulation in liverrdquoFood and Chemical Toxicology vol 50 no 6 pp 2070ndash20732012

[79] E O Salawu A A Adeleke O O Oyewo et al ldquoPreventionof renal toxicity from lead exposure by oral administration ofLycopersicon esculentumrdquo Journal of Toxicology and Environ-mental Health Sciences vol 1 no 2 pp 22ndash27 2009

[80] J Shi and M Le Maguer ldquoLycopene in tomatoes chemicaland physical properties affected by food processingrdquo CriticalReviews in Food Science and Nutrition vol 40 no 1 pp 1ndash422000

[81] A Tito A Carola M Bimonte et al ldquoA tomato stem cellextract containing antioxidant compounds andmetal chelatingfactors protects skin cells from heavy metal-induced damagesrdquoInternational Journal of Cosmetic Science vol 33 no 6 pp 543ndash552 2011

[82] A Barzegar and A A Moosavi-Movahedi ldquoIntracellular ROSprotection efficiency and free radical-scavenging activity ofcurcuminrdquo PLoS ONE vol 6 no 10 Article ID e26012 2011

[83] B A Sutherland R M A Rahman and I Appleton ldquoMecha-nisms of action of green tea catechins with a focus on ischemia-induced neurodegenerationrdquo The Journal of Nutritional Bio-chemistry vol 17 no 5 pp 291ndash306 2006

[84] E A Hamed A-R M A Meki and N A Abd El-MottalebldquoProtective effect of green tea on lead-induced oxidative damagein ratrsquos blood and brain tissue homogenatesrdquo Journal of Physiol-ogy and Biochemistry vol 66 no 2 pp 143ndash151 2010

[85] G Kaushik S Satya and S N Naik ldquoGreen tea protec-tive action against oxidative damage induced by xenobioticsrdquoMediterranean Journal of Nutrition and Metabolism vol 4 no1 pp 11ndash31 2011

[86] EMitra A K Ghosh DGhosh et al ldquoProtective effect of aque-ous Curry leaf (Murraya koenigii) extract against cadmium-induced oxidative stress in rat heartrdquo Food and ChemicalToxicology vol 50 no 5 pp 1340ndash1353 2012

[87] V C Pires A P B Gollucke D A Ribeiro L Lungato VDrsquoAlmeida and O Aguiar Jr ldquoGrape juice concentrate protectsreproductive parameters ofmale rats against cadmium-induceddamage a chronic assayrdquo British Journal of Nutrition vol 110no 11 pp 2020ndash2029 2013

[88] P Chinthana and T Ananthi ldquoProtective effect of Solanumnigrum and Solanum trilobatum aqueous leaf extract on leadinduced neurotoxicity in albino micerdquo Journal of Chemical andPharmaceutical Research vol 4 no 1 pp 72ndash74 2012

[89] AMohy-Ud-Din Z-U Khan M Ahmad andM A KashmirildquoChemotaxonomic value of alkaloids in Solanum nigrum com-plexrdquo Pakistan Journal of Botany vol 42 no 1 pp 653ndash6602010

[90] S K Zaidi M N Hoda S Tabrez et al ldquoProtective effectof Solanum nigrum leaves extract on immobilization stressinduced changes in ratrsquos brainrdquo Evidence-Based Complementaryand Alternative Medicine vol 2014 Article ID 912450 7 pages2014

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


Acetylcholinesteraseneuromuscular junctionspreganglionic neurons of thesympathetic nervous systembasal forebrain and brainstem complexes the receptorfor the merocrine sweat glands

5-HT (serotonin or 5-ydroxytryptamine (5-HT)ATP CGRP (calcitonin gene related peptide)dopamine GABA (120574-aminobutyric acid) GnRH (gonadotropin-releasing hormone)no (nitric oxide or nitrogenoxide or nitrogen monoxide) NPY (neuropeptide Y)VIP (vasoactive intestinal peptide)GnRH and substance P

Cholinergic system

Non-cholinergic system

Alzheimerrsquos and Parkinsonrsquos diseases

Mercury arseniccadmium and lead

Heavy metals

Figure 1 Effect of heavy metals on the cholinergic and noncholinergic systems associated to Alzheimerrsquos and Parkinsonrsquos diseases

the current account of phytochemicals mediated protectionfrom neurotoxicity induced by certain heavy metals in ani-mals including humans

2 Heavy Metals Influencing Cholinergic andNoncholinergic Systems

Heavy metals are shown to adversely influence the functionsof cholinergic and noncholinergic systemsThe association ofsuch impact of heavy metals with generation of Alzheimerrsquosand Parkinsonrsquos diseases has been documented A cholinergicsystem the most significant modulators of neurotransmis-sion systems in the brain regulates physiological and cogni-tive functions such as memory learning neuronal develop-ment and differentiation [4 5] Any substance or ligands hav-ing ability to produce alter or release acetylcholine or mimicits functions at the specific acetylcholine receptor type is cat-egorized as a cholinergic Similarly any receptor or synapseusing acetylcholine as a neurotransmitter is cholinergicThe parasympathetic nervous system or the preganglionicneurons of the sympathetic nervous system neuromuscularjunctions the basal forebrain brain stem and the receptorfor the merocrine sweat glands are also cholinergic sinceacetylcholine is involved in their functions On the otherhand the noncholinergic system involving a nonnoradrener-gic noncholinergic neurotransmitter (NANC) belongs to theautonomic nervous system (ANS) and includes serotonin or5-hydroxytryptamine (5-HT) ATP Calcitonin gene relatedpeptide (CGRP) Dopamine 120574-aminobutyric acid (GABA)Gonadotropin-releasing hormone (GnRH) nitric oxide ornitrogen oxide or nitrogen monoxide (NO) NeuropeptideY (NPY) Vasoactive intestinal peptide (VIP) and substanceP The heavy metals may form complexes with these cel-lular factors containing oxygen nitrogen or sulphur and

the resultant chemical species may produce toxicity whichmight lead to themodification in proteinrsquos structure or changein enzyme system cellular dysfunction and finally death ofthe cell The effects of heavy metals on the cholinergic andnoncholinergic systems are summarized in Figure 1

21 Mercury (Hg) All the natural forms of mercury (physicaland chemical forms) can produce toxic effect at high dosesThere are so many different forms of mercury which includesinorganic mercurous (Hg II) elemental mercury vapour(Hg) mercuric (Hg III) and organic mercuric compounds[33] which have toxic effects in organs like brain lungsand kidney [34] Natural mercury is present in liquid formwhen its oxidation state is zero It is categorized in transitionmetal element inmodern periodic table and is highly reactiveand toxic The chemistry of mercury its chemical typestheir metabolic transformations in different organs variedtoxic effects in mammalian systems and possible reactionmechanisms have been recently reviewed by Sharma et al(2014) [2] The toxicity of mercury is known to be mediatedby its binding with the thiol group of cellular proteins andenzymes which disrupts the cellular physiology in brainand other organs The pathophysiology of mercury toxicityrelates with the exposure of an individual by all the threeforms (solid liquid and gas) of this heavy metal Elemen-tal mercury crosses the blood brain barrier (BBB) readilywhere it concentrates in neuronal dense bodies of lysosomesand finally leads to neurotoxicity The symptoms of mer-cury toxicity include gastrointestinal disorders headachememory loss depression hypertension and neuromuscularpains in both adults and children The therapy of mer-cury poisoning has been advised to be done with differ-ent compounds including 23-dimercapto-1-propanesulfonicacid (DMPS) D-penicillamine (DPCN) dimercaprol (BAL)







[8 9]



[10 11]

Curcumin Turmeric


[12ndash15]




[17]

Quercetin


forth


[18ndash23]






[22 28]






















4 Conclusion













Acknowledgments


References






































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology







[8 9]



[10 11]

Curcumin Turmeric


[12ndash15]




[17]

Quercetin


forth


[18ndash23]






[22 28]






















4 Conclusion













Acknowledgments


References






































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

















4 Conclusion













Acknowledgments


References






































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology









4 Conclusion













Acknowledgments


References






































































































Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology












Acknowledgments


References






































































































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








Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

Documents

Phytochemicals Mediated Remediation of Neurotoxicity Induced by