ACETAMINOPHEN-INDUCED GLUTATHIONE DEPLETION IN DIABETIC RATS

Abstract

The time course of acetaminophen-induced hepatic glutathione depletion and recovery in control and streptozotocin-diabetic female rats was studied. Initial hepatic glutathione levels were significantly higher in control animals. After a 1 g/kg i.p. dose of acetaminophen maximum depletion of reduced glutathione (GSH) occurred within 2 h in diabetics and then began to increase; maximum GSH depletion occurred at .apprx. 4 h in controls and did not begin to return to normal until after 12 h. The time course for changes in hepatic oxidized glutathione (GSSG) after acetaminophen administration followed that for GSH in both control and diabetic rats. Diurnal variations in hepatic glutathione levels do occur but they cannot explain the changes which occur after acetaminophen administration or the differences seen between control and diabetic rats. Diabetic rats are more susceptible to the glutathione depleting effects of high-dose acetaminophen; apparently the diabetic may be less able to detoxify drugs and foreign chemicals.