Dose-dependent antioxidant function of resveratrol demonstrated via modulation of reactive oxygen species in normal human skin fibroblasts in vitro.

The study of free radicals is particularly relevant in the context of human skin carcinogenesis and photoaging because of their ability to induce DNA mutations and damaging lipid peroxidation byproducts. Therefore, it is important to identify and evaluate agents with the ability to modulate intracellular free radicals. Significant interest exists in evaluating the chemotherapeutic and anti-oxidant properties of resveratrol (trans-3,4',5-trihydroxystilbene). Resveratrol is a phytoalexin, a naturally occurring compound derived from the skin of grapes and other plants. Resveratrol was selected for evaluation because of demonstrated chemopreventive and chemotherapeutic properties in a murine skin cancer model and other human cancer models through a variety of mechanisms. However, the intracellular anti-oxidant properties of resveratrol on free radicals in human skin cells in vitro is not well characterized. The purpose of this research is to investigate the ability of resveratrol to modulate the hydrogen peroxide-induced upregulation of reactive oxygen species (ROS) free radicals in normal human skin fibroblast cells in vitro. Hydrogen peroxide is a well known generator of free radicals that occurs during endogenous and UV-induced oxidation processes in the human skin and was used to upregulate ROS in normal human skin fibroblast cells. Using a flow cytometry-based assay, the results demonstrate highly significant (P<0.001) dose-dependent reduction of intracellular hydrogen peroxide-upregulated ROS by resveratrol at 0.01%, 0.001% and 0.0001% concentrations in human skin fibroblasts in vitro.