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The present study was undertaken to examine whether the oxidative effect of organic hydroperoxide on cultured rat hepatocytes is enhanced by eicosapentaenoic acid (EPA). The cells were pretreated with 0.8 mM EPA which was complexed to bovine serum albumin (EPA-BSA) for 4 h, and then challenged to cumene hydroperoxide (CMHP). By the addition of CMHP to the cell culture, lipid peroxidation estimated as production of malondialdehyde (MDA) was provoked to a much greater extent in the EPA-loaded hepatocytes than in the non-loaded cells. The CMHP treatment also resulted in more severe cell injury in association with the decrease in intracellular levels of glutathione and protein thiols in the EPA-loaded cells as compared with results in the non-loaded cells. The addition of antioxidants such as N,N'-diphenyl-p-phenylenediamine (DPPD), promethazine and gamma-tocopherol to the culture medium prevented the CMHP-induced oxidative injury effectively for the EPA-loaded cells but had little effect for the non-loaded cells. The potency of other unsaturated fatty acids with different numbers of double bonds in enhancing the CMHP-induced lipid peroxidation and injury was also examined. The deleterious effects of CMHP were little affected by unsaturated fatty acids with one or two double bonds but were markedly intensified by those with more than 4 double bonds. These data showed that the supplementation with highly unsaturated fatty acids makes the cells susceptible to the drug-induced oxidative stress.

Effect of Cumene Hydroperoxide on Lipid Peroxidation in Cultured Rat Hepatocytes Supplemented with Eicosapentaenoic Acid.