Activities of Liver Microsomal Drug-Metabolizing Enzymes by Oral Administration of Thiabendazole(TBZ) to Male and Female Mice.

Abstract

Enzyme activities of liver microsomal cytochromes P-450 induced by thiabendazole (TBZ) which has been used as a food additive were investigated in 5 and 11 week-old mice (male and female). TBZ was suspended in olive oil and mice were given orally at 350, 700 or 1000 mg/kg/d for 3 d. Cytochromes P-450 were purified from mice liver microsomes by EAH Sepharose 4B and DEAE Sephadex A-50 chromatography. The catalytic activities of mice liver microsomes and purified cytochromes P-450 fractions on TBZ, aniline, aminopyrine and biphenyl were examined. TBZ hydroxylase, aniline hydroxylase and biphenyl 4-hydroxylase of liver microsomes were induced by TBZ in mice, but aminopyrine N-demethylase was not induced. TBZ hydroxylase activity was higher in female than male in 11 week-old mice. In a reconstituted system of cytochromes P-450, the fractions from TBZ-treated mice showed higher activities of TBZ and aniline hydroxylases than the corresponding fractions from untreated mice.