Protective effect of lipophilic derivatives of ascorbic acid on lipid peroxide-induced endothelial injury

The protective effects of ascorbic acid and its lipophilic derivatives on the cytotoxicity of linoleic acid hydroperoxide (LOOH), a primary product of lipid peroxidation, was investigated in cultured human umbilical vein endothelial cells. When cells were incubated with ascorbic acid for 24 h before treatment with LOOH, ascorbic acid did not protect cells from oxidative damage by LOOH. Its lipophilic derivatives such as 6-O-palmitoyl,6-O-stearoyl, and 2,6-O-dipalmitoyl esters and 2-O-octadecyl ether (CV3611) had an apparent protective effect on the toxicity of LOOH. When cells were incubated in medium containing both antioxidant and LOOH, the protective effect of lipophilic derivatives became weak. An interaction between alpha-tocopherol and ascorbic acid was not observed in this system using endothelial cells. However, in the case where the cells were preincubated with alpha-tocopherol and 6-O-palmitoylascorbic acid, the ascorbic acid derivative had a synergistic effect to alpha-tocopherol in protecting against LOOH-induced damage. These results suggest that lipophilic antioxidants incorporated into cellular membranes are effective protectors against LOOH, whereas lipophobic antioxidants located outside the membrane do not have any protective effect.