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Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes

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Author: Price, R.J. · Scott, M.P. · Walters, D.G. · Stierum, R.H. · Groten, J.P. · Meredith, C. · Lake, B.G.
Institution: TNO Voeding
Source:Food and Chemical Toxicology, 6, 42, 899-908
Identifier: 237780
doi: doi:10.1016/j.fct.2004.01.013
Keywords: Nutrition · Physiological Sciences · 1-chloro-2,4-dinitrobenzene · BHT · Butylated hydroxytoluene · CDNB · CH · Cumene hydroperoxide · CYP · Cytochrome P450 · DCNB · Enzyme induction · GSH S-transferase · Rat liver · Thiabendazole · Xenobiotic metabolism · apoprotein · butylcresol · cytochrome P450 1A · cytochrome P450 1A1 · cytochrome P450 1A2 · cytochrome P450 2B · cytochrome P450 2B1 · cytochrome P450 2B2 · glutathione transferase · messenger RNA · tiabendazole · animal cell · animal experiment · article · controlled study · dose response · drug megadose · enzyme activation · enzyme activity · enzyme induction · enzyme metabolism · enzyme substrate · liver microsome metabolism · liver mitochondrion · liver weight · male · nonhuman · nucleotide sequence · protein blood level · rat · xenobiotic metabolism · Acyltransferases · Administration, Oral · Animals · Antinematodal Agents · Antioxidants · Butylated Hydroxytoluene · Cytochrome P-450 Enzyme System · Dose-Response Relationship, Drug · Glutathione Transferase · Liver · Male · Rats · Rats, Sprague-Dawley · RNA, Messenger · Thiabendazole


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.