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 S-transferase (GST) catalyzed conjugation with 1-chloro-2,4-dinitrobenzene (CDNB) (Phase II reaction) was evaluated in diabetic rats sacrificed 3 weeks after alloxan treatment (2 doses of 75 mg/kg at an interval of 48 h, i.p.). Alloxan treatment caused 3-4 fold increase in blood glucose 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 rats as compared with the controls. The activity of GST was also significantly reduced in liver and kidney, whereas remained unchanged in the brain. These results suggest that a prolonged diabetic state depresses the metabolism of xenobiotics and probably of some endogenous compounds as well in liver and kidney.