Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes
article
The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets containing 1457 and 10,155 ppm butylated hydroxytoluene (BHT). Treatment with TB and BHT resulted in dose-dependent increases in relative liver weight. TB was found to be a mixed inducer of cytochrome P450 (CYP) forms in the CYP1A and CYP2B subfamilies. The administration of high doses of TB resulted in the induction of 7-ethoxyresorufin O-deethylase and 7-pentoxyresorufin O-depentylase activities, CYP1A1, CYP1A2, CYP2B1 and CYP2B1/2 mRNA levels and CYP1A2 and CYP2B1/2 apoprotein levels. In contrast, BHT was a CYP2B form inducer, increasing 7-pentoxyresorufin O-depentylase activity, CYP2B1 and CYP2B1/2 mRNA levels and CYP2B1/2 apoprotein levels. Both TB and BHT induced GSH S-transferase activities towards a range of substrates. In addition, TB and BHT markedly induced GSTP1 mRNA levels, but had only a small effect on GSTT1 mRNA levels. In summary, these results demonstrate that TB induces both phase I and II xenobiotic metabolising enzymes in rat liver. © 2004 Elsevier Ltd. All rights reserved.
Topics
Physiological Sciences1-chloro-2,4-dinitrobenzeneBHTButylated hydroxytolueneCDNBCHCumene hydroperoxideCYPCytochrome P450DCNBEnzyme inductionGSH S-transferaseRat liverThiabendazoleXenobiotic metabolismApoproteinButylcresolCytochrome P450 1ACytochrome P450 1A1Cytochrome P450 1A2Cytochrome P450 2BCytochrome P450 2B1Cytochrome P450 2B2Glutathione transferaseMessenger RNATiabendazoleAnimal cellAnimal experimentControlled studyDose responseDrug megadoseEnzyme activationEnzyme activityEnzyme inductionEnzyme metabolismEnzyme substrateLiver microsome metabolismLiver mitochondrionLiver weightMaleNonhumanNucleotide sequenceProtein blood levelRatXenobiotic metabolismAcyltransferasesAdministration, OralAnimalsAntinematodal AgentsAntioxidantsButylated HydroxytolueneCytochrome P-450 Enzyme SystemDose-Response Relationship, DrugGlutathione TransferaseLiverMaleRatsRats, Sprague-DawleyRNA, MessengerThiabendazole
TNO Identifier
237780
ISSN
02786915
Source
Food and Chemical Toxicology, 42(6), pp. 899-908.
Pages
899-908
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