CYTOCHROME P450-DEPENDENT OXIDATION AND GLUTATHIONE CONJUGATION OF XENOBIOTICS IN ALLOXAN-INDUCED DIABETIC RAT

The status of cytochrome P450-dependent oxidative biotransformation of aminopyrine and benzo(a)pyrene (Phase I reaction) and glutathione 8-t ransferase (GST) catalyzed conjugation with 1-chloro-2,4-dinitrobenzen e (CDNB) (Phase II reaction) was evaluated in diabetic rats sacrificed 3 weeks after alloxan treatment (2 doses of 75 mg/kg at an interval o f 48 h, i.p.). Alloxan treatment caused 3-4 fold increase in blood glu cose level and 68% rise in glycosylated hemoglobin content. There were significant decreases in the activities of the hepatic aminopyrine N- demethylase and aromatic hydrocarbon hydroxylase (AHH) in diabetic rat s as compared with the controls. The activity of GST was also signific antly reduced in liver and kidney, whereas remained unchanged in the b rain. These results suggest that a prolonged diabetic state depresses the metabolism of xenobiotics and probably of some endogenous compound s as well in liver and kidney.