Comparison of the effects of alloxan and streptozotocin on hepatic drug metabolism in rats

Abstract

The comparative effects of alloxan (120 mg kg -1 , s.c.) and streptozotocin (55 mg kg -1 , i.p.) on hepatic drug metabolism were studied in male Wistar rats over a period of two weeks. Fasting the animals for 24 h before and 6 h after the administration of either diabetogen was found to be the optimum condition for the induction of chemical diabetic state. Under this condition, both groups of diabetic animals showed a significant reduction in the metabolism of type I substrates (aminopyrine and hexobarbital) in vitro and this effect was observed after 2 days of treatment with either diabetogen. In contrast, the hepatic metabolism of type II compounds (aniline and p-chloro-N-methyl-aniline) and reverse type I substrate (p-nitroanisole) was enhanced in these two groups of the diabetic rats. Further studies using actinomycin D suggested that the stimulatory effect of alloxan and streptozotocin on the hepatic metabolism of aniline and p-nitroanisole was almost likely due to a new synthesis of the drug-metabolizing enzymes, in as much as this effect was completely blocked by pretreatment with this inhibitor of protein biosyntheis. It was concluded that there was no significant difference between the effects of alloxan and streptozotocin on blood glucose and hepatic drug-metabolizing enzymes, except only and early onset of the streptozotocin effects.