Acetaminophen-induced glutathione depletion in diabetic rats

The time course of acetaminophen-induced hepatic glutathione depletion and recovery in control and streptozotocin-diabetic female rats was investigated. Initial hepatic glutathione levels were significantly higher in control animals. After a 1 g/kg intraperitoneal dose of acetaminophen, maximum depletion of reduced glutathione (GSH) occurred within 2 h in diabetics and began to increase thereafter, while maximum GSH depletion occurred at approx. 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 these variations can not explain the changes which occur following acetaminophen administration or the differences observed between control and diabetic rats. Diabetic rats are more susceptible to the glutathione depleting effects of high-dose acetaminophen, suggesting that the diabetic may be less able to detoxify drugs and foreign chemicals.