EFFECT OF CUMENE HYDROPEROXIDE ON LIPID-PEROXIDATION IN CULTURED RAT HEPATOCYTES SUPPLEMENTED WITH EICOSAPENTAENOIC ACID

The present study was undertaken to examine whether the oxidative effe ct of organic hydroperoxide on cultured rat hepatocytes is enhanced by eicosapentaenoic acid (EPA). The cells were pretreated with 0.8 mm EP A which was complexed to bovine serum albumin (EPA-BSA) for 4 h, and t hen challenged to cumene hydroperoxide (CMHP). By the addition of CMHP to the cell culture, lipid peroxidation estimated as production of ma londialdehyde (MDA) was provoked to a much greater extent in the EPA-l oaded hepatocytes than in the non-loaded cells. The CMHP treatment als o 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 add ition 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 bu t had little effect for the non-loaded cells. The potency of other uns aturated fatty acids with different numbers of double bonds in enhanci ng the CMHP-induced lipid peroxidation and injury was also examined. T he deleterious effects of CMHP were little affected by unsaturated fat ty acids with one or two double bonds but were markedly intensified by those with more than 4 double bonds. These data showed that the suppl ementation with highly unsaturated fatty acids makes the cells suscept ible to the drug-induced oxidative stress.