Novasil, Mycotoxin Binder

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    MycotoxinsMycotoxins andandAnimal NutritionAnimal Nutrition

    TrouwTrouw Nutrition HifeedNutrition Hifeed

    anutrec

    ocompany

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    ApakahApakah mycotoxinsmycotoxins ??

    Mycotoxins adalah racun , sisa metabolite jamur

    Fungispores

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    ApakahApakah mycotoxinsmycotoxins ??

    •Bijian•Jagung•Kacang tanah

    •Bahan baku dari tumbuhan yg lain

    Mudah terinfeksi jamur.

    Kelembaban dan panas mempengaruhi pertumbuhan jamuryg memperoduksi mikotoksin

    Silo – silo di daerah tropis memiliki mikroklimate yang idealuntuk pertumbuhan jamur, karena adanya proseskondensasi yang diakibatkan oleh tingginya fluktuasitemperatur sepanjang hari.

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    FungiFungi growthgrowth in silo’sin silo’s

    3. Jamur tumbuhkarena akumulasikelambaban padabagian atas.

    Distribusi kelembabandalam Silo :

    1. Evaporasi padasiang hari (saattemperatur tinggi )

    2. Kondensasi saat

    malam hari saattemperatur rendah

    2.

    1.

    3.

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    JenisJenis mycotoxinsmycotoxins

    Terdapat spesies jamur yang berbeda , yg menghasilkan 5group mikotoksin.

    •Aflatoxins

    •Zearalenone

    •Trichothecenes•Fumonisins

    •Ochatroxin A

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    EffekEffek masuknya mycotoxinmasuknya mycotoxin

    Mikotoksin menghambat berbagai efek biologisMikotoksin menghambat berbagai efek biologis

    dalam tubuh hewan setelah ia masuk :dalam tubuh hewan setelah ia masuk :

    •• Keracunan hati dan ginjalKeracunan hati dan ginjal

    •• Kegagalan system syaraf utamaKegagalan system syaraf utama

    •• Menyebabkan problem fertilitas dan reproduksiMenyebabkan problem fertilitas dan reproduksi

    Efek biologis terlihat dalam berbagai tingkatanEfek biologis terlihat dalam berbagai tingkatantergantung padatergantung pada

    Jumlah mikotoksin yang masukJumlah mikotoksin yang masuk

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    EffekEffek dari keracunandari keracunan

    Kerugian

    Pada ternak

    Phase 4: Kematian

    Tingkat kontaminasi mikotoksin

    Phase 1: Penurunan produktivitas; pertum

    Buhan lambat, penurunan produksi,

    Immune suppression.

    Phase 2: Kejadian penyakit meningkat

    (secondary infections) karena immune

    suppresion

    Phase 3: Gejala klinis kerusakan

    terget organ yg spesifik dengan

    type mikotoksin yg mengkontaminasi

    0

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    SOLUSI :SOLUSI : DetoxifikasiDetoxifikasi

    Terdapat 2 prinsipTerdapat 2 prinsip detoxifikasi:detoxifikasi:

    1.1. ToxinToxin--bindingbinding

    2.2. EnzymaticEnzymatic breakdownbreakdown

    Keduanya diterapkan untuk mikotoksinKeduanya diterapkan untuk mikotoksin

    yang berbeda.yang berbeda.

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    1.1. ToxinToxin--bindingbinding

    •• Didasarkan pada polaritas elektrik toksin.Didasarkan pada polaritas elektrik toksin.

    •• ToxinToxin akan diikat oleh toxinakan diikat oleh toxin bindersbinders untukuntuk

    mencegah absorbsi yg dilakukan oleh saluranmencegah absorbsi yg dilakukan oleh salurancerna.cerna.

    TOX.

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    2.2. EnzymaticEnzymatic breakdownbreakdown

    •• Berdasarkan konversi enzimatik toksinBerdasarkan konversi enzimatik toksin

    TOX.

    TOX.

    ENZYME

    TOX.

    TOX.

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    Kapan dan harus menggunakanKapan dan harus menggunakan

    apa..???apa..???

    Dua prinsip detoksifikasi seharusnya digunakanDua prinsip detoksifikasi seharusnya digunakan

    pada situasi yang benar.pada situasi yang benar.

    Binding/ Pengikatan :Binding/ Pengikatan :

    •• Digunakan untukDigunakan untuk AflatoxinsAflatoxins andand OchratoxinOchratoxin A,A,

    karena sifatkarena sifat electricelectric polarity toksinpolarity toksin

    EnzymaticEnzymatic breakdown:breakdown:

    •• Digunakan untuk mykotoksin yg lain.Digunakan untuk mykotoksin yg lain.

    ((ZearalenoneZearalenone,, TrichothecenesTrichothecenes,, FumonisinsFumonisins))

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    PresencePresence ofof toxinstoxins in thein the worldworld

    OthersAflatoxins

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    What products canWhat products can TrouwTrouw

    NutritionNutrition offeroffer youyou??

    Mengatasi aflatoxinsMengatasi aflatoxins dan ochratoxinsdan ochratoxins::

    Mengatasi semua Mycotoksin :Mengatasi semua Mycotoksin :

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    WhatWhat isis ??

    •• NamaNama Generic Hydrated Sodium CalciumGeneric Hydrated Sodium Calcium

    AluminosilicateAluminosilicate (HSCAS)(HSCAS)

    •• LebihLebih spesifikspesifik ,, dikenaldikenal sebagaisebagai CalciumCalciumMontmorilloniteMontmorillonite

    •• SumberSumber mineralmineral alamialami ;; MenggunakanMenggunakanteknologiteknologi ygyg tepattepat,, ketersediaanketersediaan,,

    ditambangditambang,, diprosesdiproses dgndgn telititeliti

    •• ProdukProduk akhirakhir memilikimemiliki luasluas permukaanpermukaaninternal > 1,000 meterinternal > 1,000 meter--persegipersegi per gramper gram

    y

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    How doesHow does NovasilplusNovasilplus work?work?

    •• When it’s in solution; I.e.When it’s in solution; I.e.when taken in by thewhen taken in by theanimalanimal

    •• (left picture)(left picture) ScanningScanningelectron micrograph ofelectron micrograph ofproductproduct (a(a spongelikespongelike PSC thatPSC thatbindsbinds aflatoxinsaflatoxins in the GI tract ofin the GI tract ofanimals) 4,500 xanimals) 4,500 x

    •• The interaction withThe interaction withCalcium (metal ion) in theCalcium (metal ion) in theinterlamellarinterlamellar region,region,being the major part ofbeing the major part of

    the adsorption ofthe adsorption ofmycotoxinsmycotoxins to theto theNovasilplusNovasilplus formationformationof aof a chelatechelate

    y

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    SITES OF AfB1 ADSORPTION TO1

    NOVASILPLUS

    Edge site

    Edge site

    Interlayer

    surface

    Basal surface

    y

    DOCKING AND CHELATION OF AFB AT

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    DOCKING AND CHELATION OF AFB1

    METAL EDGE SITES IN NOVASILPLUS

    1 AT

    Chelation of metal ions in Novasil

    by the  β -dicarbonyl moiety in AfB 1

     Aflatoxin B1

    O

    O

    O

    O CH3O

    O

    M

    H

    H

    Chemical structure

    Novasilplus

     AfB1

    MOLECULAR VISUALIZATION OF PROPOSED EDGE SITE MECHANISM

    y

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    KenapaKenapa ??

    Penelitian independent telahPenelitian independent telah

    membuktikan bahwa NovaSil plus adalahmembuktikan bahwa NovaSil plus adalah

    binder aflatoxin terbaik di dunia...binder aflatoxin terbaik di dunia...

    y

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    Novasil/NovasilplusNovasil/Novasilplus ResearchesResearches (1)(1)

    AnimalAnimal

    TypeTypeMycotoxinMycotoxin Research TypeResearch Type Who did itWho did it WhatWhat

    PublicationPublication

    ChickensChickens AflatoxinAflatoxin B1,B1,

    up to 3.5ppmup to 3.5ppm

    && OchratoxinOchratoxinA1 up to 2ppmA1 up to 2ppm

    In Vivo USDA/UniversityIn Vivo USDA/University

    trialstrialsDr. TD PhillipsDr. TD Phillips –– TAMUTAMU

    Dr. LFDr. LF KubenaKubena, Dr. RB, Dr. RB

    Harvey & Dr. WE HuffHarvey & Dr. WE Huff–– USDAUSDA

    1992 Poultry1992 Poultry

    Science 71; 64Science 71; 64--

    6969

    ChickensChickens AflatoxinAflatoxin B1,B1,

    up to 3.5ppmup to 3.5ppm

    & DAS up to& DAS up to

    5ppm5ppm

    In Vivo USDA/UniversityIn Vivo USDA/University

    trialstrialsDr. TD PhillipsDr. TD Phillips –– TAMUTAMU

    Dr. LFDr. LF KubenaKubena et alet al ––

    USDAUSDA

    Dr. GEDr. GE RottinghausRottinghaus ––University of MissouriUniversity of Missouri

    1993 Poultry1993 Poultry

    Science 72; 51Science 72; 51--

    5959

    ChickensChickens NoNo mycotoxinmycotoxin

    contaminationcontaminationIn Vivo University trials;In Vivo University trials;

    check if any negativecheck if any negative

    effects from addition ofeffects from addition of

    Novasil to dietsNovasil to diets

    Dr. DH Baker & Dr. TKDr. DH Baker & Dr. TK

    ChungChung –– University ofUniversity of

    IllinoisIllinois

    J.J. AnimAnim.. SciSci..

    1990; 68: 19921990; 68: 1992--

    19981998

    ChickensChickens AflatoxinAflatoxin B1 upB1 upto 3.5ppmto 3.5ppm

    In Vivo USDA/UniversityIn Vivo USDA/Universitytrials; also to check iftrials; also to check if

    any negative effects fromany negative effects from

    addition of Novasil toaddition of Novasil to

    diets withdiets with VirginiamycinVirginiamycin

    Dr. TD PhillipsDr. TD Phillips –– TAMUTAMU

    Dr. LFDr. LF KubenaKubena et alet al ––

    USDAUSDA

    1995 Poultry1995 PoultryScience 74; 626Science 74; 626--

    632632

    y

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    Novasil/NovasilplusNovasil/Novasilplus ResearchesResearches (2)(2)

    AnimalAnimal

    TypeType

    MycotoxinMycotoxin ResearchResearchTypeType

    Who did itWho did it What PublicationWhat Publication

    Studies InStudies In

    Vitro &Vitro &

    then Inthen In

    VivoVivostudiesstudies

    withwith

    ChickensChickens

    AlfatoxinAlfatoxin B1,B1,

    up to 7.5ppmup to 7.5ppmRadioactivityRadioactivity

    labeledlabeled

    markers formarkers for

    adsorptionadsorptiontests; in vitrotests; in vitro

    (TLC) and in(TLC) and in

    vivovivo

    Dr. Timothy PhillipsDr. Timothy Phillips

    –– TAMUTAMU

    Dr.LeonDr.Leon KubenaKubena &&

    Dr. Roger HarveyDr. Roger Harvey ––USDAUSDA

    !988 Poultry Science 67;!988 Poultry Science 67;

    243243--247247

    Vet. HumVet. Hum ToxicolToxicol 3232

    (Supplement) 1990; 15(Supplement) 1990; 15--1919Natural Toxins 3; 204Natural Toxins 3; 204--213213

    (1995)(1995)

    The Toxicology ofThe Toxicology of AflatoxinsAflatoxins;;

    383383--406406

    ChickensChickens AflatoxinAflatoxin B1 upB1 upto 7.5ppmto 7.5ppm

    In Vivo USDA/In Vivo USDA/UniversityUniversity

    trialstrials

    Dr. Timothy Phillips,Dr. Timothy Phillips,Dr. DEDr. DE CorrierCorrier & Dr.& Dr.

    WE HuffWE Huff –– TAMUTAMU

    Dr. LFDr. LF KubenaKubena & Dr.& Dr.

    RB HarveyRB Harvey –– USDAUSDA

    1990 Poultry Science 69;1990 Poultry Science 69;727727--735735

    ChickensChickens AflatoxinAflatoxin B1 upB1 up

    to 5ppmto 5ppm

    In Vivo USDA/In Vivo USDA/

    UniversityUniversitytrialstrials

    Dr. TD Phillips & Dr.Dr. TD Phillips & Dr.

    BA ClementBA Clement –– TAMUTAMUDr. LFDr. LF KubenaKubena & Dr.& Dr.

    RB HarveyRB Harvey –– USDAUSDA

    1993 Poultry Science 72;1993 Poultry Science 72;

    651651--657657

    ny

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    Novasil/NovasilplusNovasil/Novasilplus ResearchesResearches (3)(3)

    AnimalAnimal

    TypeTypeMycotoxinMycotoxin Research TypeResearch Type Who did itWho did it WhatWhat

    PublicationPublication

    ChickensChickens AflatoxinAflatoxin B1,B1,

    up to 3.5ppmup to 3.5ppm

    & T& T--2 toxin (T2 toxin (T--

    2) up to 8ppm2) up to 8ppm

    In Vivo USDA/UniversityIn Vivo USDA/University

    trialstrialsDr. TD PhillipsDr. TD Phillips ––

    TAMUTAMU

    Dr. LFDr. LF KubenaKubena et alet al ––

    USDAUSDA

    Dr. GEDr. GE RottinghausRottinghaus ––

    University of MissouriUniversity of Missouri

    1990 Poultry1990 Poultry

    Science 69; 1078Science 69; 1078--

    10861086

    TurkeysTurkeys AflatoxinAflatoxin, up to, up to

    1ppm1ppmIn Vivo USDA/UniversityIn Vivo USDA/University

    trialstrialsDr. TD PhillipsDr. TD Phillips ––

    TAMUTAMU

    Dr. LFDr. LF KubenaKubena et alet al ––USDAUSDA

    1991 Poultry1991 Poultry

    Science 70; 1823Science 70; 1823--

    18301830

    MinkMink ZearalenoneZearalenone

    up to 20ppmup to 20ppmIn Vivo University trialsIn Vivo University trials SJSJ BusianBusian, RJ, RJ

    AulerichAulerich, JK Cameron,, JK Cameron,

    NK Ames & BANK Ames & BA

    SteficekSteficek –– MichiganMichigan

    State UniversityState University

    Journal of AppliedJournal of Applied

    Toxicology, Vol.Toxicology, Vol.

    12(2); 8512(2); 85--9090

    (1990)(1990)

    LambsLambs AflatoxinAflatoxin up toup to

    2.6ppm2.6ppmIn Vivo USDA/UniversityIn Vivo USDA/University

    trialstrialsDr. TD Phillips et alDr. TD Phillips et al ––

    TAMUTAMU

    Dr. LFDr. LF KubenaKubena et alet al ––

    USDAUSDA

    American JournalAmerican Journal

    of Veterinaryof Veterinary

    Research, Vol. 52,Research, Vol. 52,

    No. 1; 152No. 1; 152--156156

    (January 1991)(January 1991)

    ny

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    UnmatchedUnmatched bindingbinding capacitycapacity

    Publicated by

    Dr. Pimdukdee

    of the

    Khon Kaen

    University

    Thailand in

    “Thailand Feed

    and Livestock”

    December 2003

    ny

    There are too many products in theThere are too many products in the

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    compan There are too many products in theThere are too many products in the

    market, how to make a good choice?market, how to make a good choice?

    •• What’s the material;What’s the material;

    Kaolin,Kaolin, ZeoliteZeolite, Sodium, Sodium

    BentoniteBentonite or Calciumor Calcium

    MontmorilloniteMontmorillonite??•• Is the mine(s) andIs the mine(s) and

    processing plant(s)processing plant(s)

    known?known?

    •• How much researches,How much researches,

    especially Inespecially In--Vivo ones,Vivo ones,

    had been done?had been done?

    •• How much have theHow much have theproducts passed experts’products passed experts’

    previews?previews? –– What JournalWhat Journal

    Publications?Publications?

    ny

    O O O O CPREVENTION OF HEPATOTOXICITY

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    PREVENTION OF HEPATOTOXICITY

    IN CHICKS BY HSCAS

    PREVENTION OF HEPATOTOXICITY

    IN CHICKS BY HSCAS

    AfB 1  + 0.5% HSCAS AfB 1 (7.5 ppm) 

    MECHANISM OF ACTION:

    Adsorption of aflatoxins in the gastrointestinal tractand decrease in bioavailability to the blood and

    tissues.

    References: Phillips, T.D. et al. (1988). Poult. Sci. 67:243-247.

      Phillips, T.D. et al. (1994). Toxicology of Aflatoxins, Academic Press, pp. 383-406.

    ny

    AFLATOXIN-INDUCED HEPATOTOXICITYAFLATOXIN-INDUCED HEPATOTOXICITY

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    compan  AFLATOXIN INDUCED HEPATOTOXICITY

    IN PIGS: PROTECTION WITH HSCAS

     AFLATOXIN INDUCED HEPATOTOXICITY

    IN PIGS: PROTECTION WITH HSCAS

    Aflatoxin Control  AfL + 0.5% HSCAS 

    PHOTOMICROGRAPHS OF LIVER PHOTOMICROGRAPHS OF LIVER 

    Hepatic portal triad

    showing fibrosis (Left)

    and protection (Right) 

    References: Harvey et al. (1989). Am. J. Vet. Res. 50:416-420.

      Harvey et al. (1994). J. Vet. Diagn. Invest. 6:88-92.

    ny EFFECTS OF AFLATOXIN AND SORBENTSEFFECTS OF AFLATOXIN AND SORBENTS

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    Experimental Treatments

    0

    20

    40

    60

    80

    100

       %    R  e

      s  o  r  p   t   i  o  n  s

    Untreated HSCAS + Corn OilZeo + Corn Oil

     AFB1 HSCAS + AFB1 Zeo + AFB!

    EFFECTS OF AFLATOXIN AND SORBENTS

    ON EMBRYOLETHALITYON EMBRYOLETHALITY

    Control A  HSCAS/A Zeo/A

     A - Aflatoxin B1

    Zeo - Zeolite (clinoptilolite)

    HSCAS - NovaSil

    Reference: Mayura et al. (1998). Toxicol. Sci. 41:175-182.

    any TAMU Studies show Novasil &TAMU Studies show Novasil & NovasilplusNovasilplus

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    compa TAMU Studies show Novasil &TAMU Studies show Novasil & NovasilplusNovasilplus

    do not bind away nutrients (Vit A)do not bind away nutrients (Vit A)

    any

    h dU h d bi dibi di ii

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    UnmatchedUnmatched bindingbinding capacitycapacity

    any

    A Look at a CrossA Look at a Cross--Section of a MineSection of a Mine

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    compa A Look at a CrossA Look at a Cross Section of a MineSection of a Mine

    Picture taken from Feed Mix Magazine,Vol.8 No.1Picture taken from Feed Mix Magazine,Vol.8 No.1 -- 20002000

    any

    I l i tI l i t d t td t t ltlt

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    Inclusion ratesInclusion rates and testand test resultsresults

    any

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    Terima kasihTerima kasih

    atas perhatian Andaatas perhatian Anda