The Antioxidant Effects of Glutathione and Ascorbic Acid

Abstract

The functions of glutathione have been explored by use of a model animal system in which the cellular synthesis of glutathione is inhibited. Glutathione deficiency, induced by administration of buthionine sulfoximine (an inhibitor of the first step of glutathione synthesis) leads to mortality in newborn rats and in guinea pigs, animals that are unable to synthesize ascorbic acid, and to tissue damage in these animals and in adult mice, which can synthesize ascorbic acid. Mortality and morbidity are greatly diminished by administration of glutathione esters or of ascorbic acid. These and other findings indicate that cellular glutathione is essential for the physiological function of ascorbic acid, that ascorbic acid can spare glutathione, and that glutathione (supplied as an ester) can spare ascorbic acid. Recent studies showed that administration of glutathione (in an ester form) to guinea pigs fed an ascorbatedeficient diet significantly delays the onset of scurvy, a disease in which oxidative stress leads to inactivation of certain enzymes that catalyze hydroxylation reactions. The present findings demonstrate that ascorbic acid and glutathione function together as an antioxidant couple. Since there is good evidence that glutathione and/or ascorbic acid function in maintaining the reduced forms of other cellular components, such as α-tocopherol, it appears that glutathione is the source of a major portion of cellular antioxidant activity.