Prostaglandins and related compounds are active
mediators of inflammation, but data concerning their role in the pathogenesis of the
glomerulonephritis of New Zealand Black x New Zealand White (NZB x NZW) F1 mice are conflicting. Dietary
eicosapentaenoic acid (EPA, C20:5), a
fatty acid analogue of
arachidonic acid (C20:4), has been shown to impair platelet aggregation in humans, apparently through inhibition of the synthesis of
prostaglandins and
thromboxanes from
arachidonic acid. We report here the effects of a diet high in EPA on the development of renal disease and survival in female NZB x NZW F1 mice. 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 less than 0.05 and 14.4% EPA, respectively. In the first 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. In contrast, none of 10
menhaden oil-fed animals had developed
proteinuria, and all were alive at this time (P less than 0.005 for both
proteinuria and survival). In a second 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 less than 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 less than 0.01). Weights were similar in all groups, and there was no evidence of essential
fatty acid deficiency in any group. These results demonstrate that a diet high in EPA protects NZB x NZW F1 mice from the development of
glomerulonephritis.