Biochemical studies on the mechanism of action of liver poisons III. Depletion of liver glutathione in ethionine poisoning

Abstract

Abstract Administration of ethionine to female rats was followed by rapid fall of the hepatic reduced glutathione content, concomitant with a progressive impairment of the cell-free protein-synthesizing capacity and a decline of the ATP level. In male rats and in adrenalectomized female rats, the onset of the first two alterations was considerably delayed. In contrast, the time course and the severity of the ethionine-induced ATP depletion were essentially the same in all instances. Treatment with CCl 4 , despite the similarity of its hepatotoxic effects to those of ethionine, resulted in no appreciable decrease of the liver reduced glutathione level. Administration of methionine counteracted both the reduced glutathione decline and the other biochemical lesions induced by ethionine, whereas injection of adenine, though preventing the ATP depletion, failed to reverse the depression of reduced glutathione. The available evidence suggests that the decrease in the reduced glutathione level reflects a diminished capacity of the liver for oxidized glutathione reduction and its resultant inability to compensate the normal process of continuous reduced glutathione oxidation. The possible role of the altered reduced glutathione metabolism in the pathogenesis of ethionine hepatotoxicity is discussed.