Protective effects of lycopene against H2O2-induced oxidative injury and apoptosis in human endothelial cells.

摘要

PURPOSE: Oxidative stress is considered to be a major factor contributing to damage of endothelial cells, and is an important component of the etiology of atherosclerosis. In this study, we investigated the effects of lycopene on the oxidative injury and apoptosis of endothelial cells induced by H(2)O(2), and the effects of lycopene on the expression of p53, caspase-3 mRNA in injured cells. METHODS: In the H(2)O(2) group, endothelial cells were incubated with 400 microM H(2)O(2). In lycopene groups, endothelial cells were pretreated with different concentrations of lycopene then exposed to 400 microM H(2)O(2). In the drug control group, cells were pretreated with probucol then incubated with H(2)O(2). The effects of different concentrations of lycopen on the extent of oxidative injury to the cells were evaluated. The growth conditions and morphological changes of the cells were observed with an inverted microscope. The level of oxidative injury to cells was determined by measuring malondialdehyde (MDA) levels; the viability of cells was detected by MTT assays; the nuclear morphology of cells was observed by Hoechst staining; the apoptotic ratio of cells was measured by flow cytometry; and the expressions of p53 and caspase-3 mRNA were investigated by RT-PCR. RESULTS: Lycopene improved the shape of contracted endothelial cells induced by H(2)O(2) injury, and diminished the level of MDA produced following oxidative injury of cells. The viability of cells increased, and the number of cells characterized by apoptotic nuclear morphology decreased in groups treated with lycopene. Similarly, lycopene significantly diminished the apoptosis ratio of oxidative injured cells, and also downregulated the expressions of p53 and caspase-3 mRNA induced by H(2)O(2). Lycopene and probucol displayed similar protective effects on endothelial cells. CONCLUSIONS: Lycopene can decrease the oxidative injury of endothelial cells induced by H(2)O(2), can attenuate the expression of p53 and caspase-3 mRNA in injured cells, and can diminish the apoptosis of injured cells. These findings possibly explain in part why lycopene can prevent atherosclerotic cardiovascular diseases.