EFFECTS OF N-3 AND N-6 FATTY-ACIDS ON THE ACTIVITIES AND EXPRESSION OF HEPATIC ANTIOXIDANT ENZYMES IN AUTOIMMUNE-PRONE NZBXNZW F1-MICE

Menhaden fish oil (FO) containing n-3 fatty acids dramatically extends the life span and delays the onset and progression of autoimmune dise ase in (NZBxNZW)F-1 (B/W) female mice as compared to those fed corn oi l (CO) rich in n-6 lipids. As an inefficient antioxidant defense syste m has been linked to autoimmune diseases, the present study was undert aken to determine whether the protective action of n-3 lipids is media ted through their antioxidant defense system. Weanling B/W mice were f ed a nutritionally adequate, semipurified diet containing CO or krill oil (KO) or FO at 10% level (w/w) ad libitum until the mice were 6.5 m onths old. All diets contained the same level of vitamin E (21.5 mg/10 0 g diet). We compared the effects of feeding n-6 and n-3 lipids on su rvival, kidney disease, hepatic microsomal lipid composition, peroxida tion, and on the activity and mRNA expression of the antioxidant enzym es catalase, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in 6.5-month-old B/W mice. The results showed that when compared to livers from CO-fed mice, livers from KO- and FO-fed mice showed: ( i) significantly higher (P < 0.001) activities and expression of CAT, GSH-Px and SOD; (ii) significantly lower (P < 0.001) arachidonic acid (20:4n-6) and linoleic acid (18:2n-6) and higher (P < 0.001) eicosapen taenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) levels in he patic microsomes; and (iii) significantly lower (P < 0.001) estimated peroxidation indices and thiobarbituric acid reactive substances gener ation. The data indicate that one of the mechanisms through which the n-3 lipids delay the onset of autoimmune diseases in B/W mice may be t hrough maintenance of higher activities and expression of hepatic anti oxidant enzymes.