Abstract

Oxidative damages to the retinal pigment epithelium (RPE) have been suggested to play a key role in the pathogenesis of age-related macular degeneration. trans-Resveratrol (3,4',5-trihydroxystilbene) is a nonflavonoid dietary polyphenol with various pharmacological effects, including antioxidant activity. The purpose of this study was to evaluate the potential protective effect of resveratrol against hydrogen peroxide induced oxidative stress in cultured human RPE cells. Human retinal D407 RPE cells were pretreated with resveratrol at 3 different concentrations (25, 50, and 100 μM) for 24 h and exposed for 1 h to 500 μM hydrogen peroxide. Cell viability, cytotoxicity, and the level of intracellular reactive oxygen species (ROS) were determined in basal and oxidative stress conditions. The concentration of reduced glutathione and the activities of catalase, superoxide dismutase, and glutathione peroxidase were also examined under both experimental conditions. Resveratrol in culture media had no cytotoxic effect at a concentration of 25-100 μM but showed a protective effect against hydrogen peroxide-induced cytoxicity. Pretreatment with resveratrol induced a significant, dose-dependent increase of superoxide dismutase, glutathione peroxidase, and catalase activities. Moreover, resveratrol significantly enhanced the level of reduced glutathione under both basal and oxidative stress conditions. The significant inhibition of the intracellular ROS generation supports the hypothesis that resveratrol can also contribute to the antioxidant defense by directly scavenging the ROS in RPE cells. Our results indicate that treatment of RPE cells with resveratrol at micromolar concentrations confers a marked protection against oxidative stress. These data suggest that dietary supplementation of resveratrol may contribute to the prevention of RPE degeneration induced by oxidative stress.

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