There is currently considerable interest in the study of cytoprotective effects of natural antioxidants against oxidative stress. However, the cellular response to oxidative stress of the antioxidants may be compromised under conditions of dietary restriction. Therefore, the objective of the present study was to investigate the ability of the (-)-epicatechin, a polyphenol with powerful antioxidant properties in vitro, to attenuate oxidative stress-induced cell damage and to understand the mechanism of its protective action in hepatocytes from overnight fasted rats. Oxidative stress in isolated hepatocytes was induced using tert-butylhydroperoxide and the cellular responses in the form of cell membrane damage, lipid peroxidation and levels of endogenous antioxidants assessed. The results provide evidence that in fasted rat hepatocytes, subjected to oxidative stress, epicatechin inhibits cell membrane damage. In addition, lipid peroxidation and superoxide dismutase and catalase activities return to their control condition. The levels of glutathione peroxidase and glutathione, however, were not significantly different from those without treatment with epicatechin, suggesting that the epicatechin influence on these intracellular antioxidants is not the mechanism of protection. (C) 2003 Elsevier Ltd. All rights reserved.