Effects of experimental diabetes on hepatic drug metabolism in rats: the activities of flavin-containing monooxygenase, the phase II conjugation reactions and glutathione related enzymes.

Abstract

Hepatic drug metabolism (flavin-containing monooxygenase (FMO), glutathione related enzymes, phase II conjugation reactions) and the hepatic contents of glutathione were investigated in normal rats, alloxan induced diabetic rats and streptozotocin (STZ) induced diabetic rats. The hepatic content of reduced or oxidized glutathione, the activities of glutathione related enzymes (glutathione reductase and glutathione peroxidase) and several enzymes (p-nitrophenol glucuronosyltransferase, aryl sulphotransferase I and II) involved in conjugation reactions were lower in alloxan- and STZ-induced diabetic rats than those in normal rats. In contrast, the activities of FMO and aryl sulphotransferase IV were significantly higher in alloxan- and STZ-induced diabetic rats than those in normal rats. Glutathione S-transferase (GST) activity also was remarkably higher in STZ-induced diabetic rats than that in normal rats. Insulin administered to STZ-induced diabetic rats prevented the hyperglycemia indicative of STZ-induced diabetes, but had no effect on the increased activities of GST. Another diabetogenic agent, alloxan, did not alter the activities of GST. On the other hand, the fluctuations in the enzymatic activities of FMO, UDP-glucuronosyltransferase, aryl sulphotransferase and glutathione related enzymes were restored to normal level by treatment with insulin in both diabetic rats. These results show that STZ may be directly increasing activities of GST, and not as a result of the diabetic state the diabetogenic agent induces. However, the fluctuations of the activities of FMO, glutathione related enzymes and some phase II reactions were dependent on diabetic states.