Inhibition of selenite cataract by S-diethylsuccinyl glutathione isopropyl ester

Abstract

Previous studies have demonstrated that glutathione derivatives can partially prevent loss of hepatic glutathione levels, in vivo, during periods of oxidative stress. Since cataracts in animal model systems and in humans are thought to be the direct result of oxidative insult, the following study tested the possibility that treatment with these glutathione analogues may affect the progression of lens opacification. Glutathione esters were tested for their ability to inhibit the selenite-induced cataract in rats. The S-alkyl glutathione ester Et(2)Sc-GS-iPr, but not a similar glutathione derivative S-succinyl glutathione (Sc-GS), at 0.5 mmoles/kg body weight, had anti-cataract activity in the selenite-induced cataract of rats. Analysis of lenses from treated and untreated animals demonstrated that Et(2)Sc-GS-iPr partially prevented the loss of reduced glutathione levels. The results demonstrate for the first time that an S-alkylated glutathione ester has anti-cataractogenic potential in the selenite-treated rat, and suggest possible mechanisms involving glutathione in the prevention of this lens opacification.