Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes.
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.
Price
Roger J
RJ
BIBRA International Ltd, Carshalton, Surrey, UK.
Scott
Mary P
MP
Walters
David G
DG
Stierum
Rob H
RH
Groten
John P
JP
Meredith
Clive
C
Lake
Brian G
BG
D000217:Acyltransferases; D000284:Administration, Oral; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002084:Butylated Hydroxytoluene; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013827:Thiabendazole / Q000008:administration & dosage / Q000494:pharmacology*
D000969:Antinematodal Agents; D000975:Antioxidants; D012333:RNA, Messenger; D002084:Butylated Hydroxytoluene; D003577:Cytochrome P-450 Enzyme System; D000217:Acyltransferases; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; C043403:fatty acyl ethyl ester synthase; D013827:Thiabendazole