LOW-DOSE EICOSAPENTAENOIC OR DOCOSAHEXAENOIC ACID ADMINISTRATION MODIFIES FATTY-ACID COMPOSITION AND DOES NOT AFFECT SUSCEPTIBILITY TO OXIDATIVE STRESS IN RAT ERYTHROCYTES AND TISSUES

In view of the promising future for use of n-3 polyunsaturated fatty a cids (PUFA) in the prevention of cancer and cardiovascular diseases, i t is necessary to ensure that their consumption does not result in det rimental oxidative effects. The aim of the present work was to test a hypothesis that low doses of eicosapentaenoic acid (EPA) or docosahexa enoic acid (DHA) do not induce harmful modifications of oxidative cell metabolism, as modifications of membrane fatty acid composition occur . Wistar rats received by gavage oleic acid, EPA, or DHA (360 mg/kg bo dy weight/day) for a period of 1 or 4 wk. Fatty acid composition and a lpha-tocopherol content were determined for plasma, red blood cell (RB C) membranes, and liver, kidney, lung, and heart microsomal membranes. Susceptibility to oxidative stress induced by tert-butylhydroperoxide was measured in RBC. EPA treatment increased EPA and docosapentaenoic acid (DPA) content in plasma and in all the membranes studied. DHA tr eatment mainly increased DHA content. Both treatments decreased arachi donic acid content and n-6/n-3 PUFA ratio in the membranes, without mo difying the Unsaturation Index. No changes in tissue alpha-tocopherol content and in RBC susceptibility to oxidative stress were induced by either EPA or DHA treatment. The data suggest that EPA and DHA treatme nts can substantially modify membrane fatty acids, without increasing susceptibility to oxidative stress, when administered at low doses. Th is opens the possibility for use of low doses of n-3 PUFA for chemopre vention without risk of detrimental secondary effects.