Docosahexaenoic acid and vitamin E can reduce human monocytic U937 cell apoptosis induced by tumor necrosis factor

The effects of polyunsaturated fatty acids and vitamin E on tumor necrosis factor (TNF)-induced apoptosis of human monocytic U937 cells was explored t o assess to what extent these nutrients could attenuate apoptosis, Preincub ation of U937 cells with arachidonic acid for 24 h did not affect TNF-induc ed apoptosis, Eicosapentaenoic acid slightly but significantly reduced the proportion of apoptotic cells only when apoptosis was induced by TNF withou t cycloheximide (CHI), In contrast, preincubation with docosahexaenoic acid (DHA) greatly (40 similar to 70%) attenuated apoptosis induced by stimulat ion with either TNF or TNF + CHI for 3 h. The inhibition of apoptosis was a ccompanied by enrichment of DHA in membrane phospholipids, indicating that DHA probably exerted its inhibitory activity after being incorporated into the phospholipids, Vitamin E also played a role as a partial inhibitor of a poptosis 3 h after TNF addition. This vitamin could further reduce the apop tosis of DHA-treated cells, and such an additive effect was obvious when ap optosis was induced at a low frequency. Longer-range stimulation of U937 ce lls with TNF showed that inhibition of apoptosis by preincubating cells wit h either DHA or vitamin E was not significant 9 h after TNF addition, but t hat preincubation with both DHA and vitamin E could reduce the proportion o f apoptotic cells even at this time point. Our findings suggested that inge stion of nutrients such as DHA and vitamin E might exert beneficial effects on organ dysfunction associated with various TN F-related diseases.