DIETARY ENRICHMENT WITH THE POLY-UNSATURATED FATTY-ACID EICOSAPENTAENOIC ACID PREVENTS PROTEINURIA AND PROLONGS SURVIVAL IN NZB X NZW F1-MICE

Prostaglandins and related compounds are active mediators of inflammation but data concerning their role in the pathogenesis of the glomerulonephritis of New Zealand Black .times. New Zealand White (NZB .times. NZW) F1 mice are conflicting. Dietary eicosapentaenoic acid (EPA, C20:5), a fatty acid analog of arachidonic acid (C20:4), impairs platelet aggregation in humans, apparently through inhibition of the synthesis of prostaglandins and thromboxanes from arachidonic acid. The effects of a diet high in EPA on the development of renal disease and survival in female NZB .times. NZW F1 mice are reported. Animals from 4-5 wk of age were fed diets containing 25% lipid, supplied either as beef tallow or menhaden oil, with fatty acid analysis of < 0.05 and 14.4% EPA. In the 1st experiment, by 13.5 mo. of age, mice on the beef tallow diet had all (9/9) developed proteinuria and the majority (6/9) had died, with renal histologic examination revealing severe glomerulonephritis. None of 10 menhaden oil-fed animals had developed proteinuria and all were alive at this time (P < 0.005 for proteinuria and survival). In a 2nd experiment using 50 mice in each dietary group, 56% of the beef tallow group vs. none of the menhaden oil group had developed proteinuria at 9 mo. of age (P < 0.005). Native DNA binding at 6 mo. of age was 23.9 .+-. 14.7 vs. 10.1 .+-. 9.7% in the beef and menhaden oil groups, respectively (P < 0.001). Weights were similar in all groups and there was no evidence of essential fatty acid deficiency in any group. A diet high in EPA protects NZB .times. NZW F1 mice from the development of glomerulonephritis.