Milan normotensive rats (MNR) develop spontaneous proteinuria, glomerulosclerosis (GS) and chronic renal failure for which there is no known therapy. Glomerular injury in MNR is a non-immune and non-toxic model of glomerular injury. The protective effects of Fish oil (FO) which reduces glomerular thromboxane A (TXA) as well as Pentoxyfylline (P) and Vitamin E(E), both antioxidants were evaluated in developing MNR since FO, P, and E are protective in toxic models of GS. Soy Oil (SO) was used for control diet. At 3 months of age, non-proteinuric MNR received 12% SO alone, 12% SO plus P(100mg/kg/day), 12% SO plus E (500 ppm) or 12% FO alone, 12% FO plus P or 12% FO plus E. Diets were isocaloric and the rats were aged matched. Results are expressed as mean ± S.E. After 5, 7 and 9 months respectively, urine protein excretion (UPE) was similar between the groups. Results after 10 months are given in the Table.

Table 1 No caption available.

Data marked B are significantly (P<0.05) different from data marked A by ANOVA. Creatinine clearances were similar between the groups. We conclude that P, FO and combined FO+P significantly reduce UPE in MNR. Moreover, Fish Oil significantly reduced serum Chol and Trigs in all rats. Reduction in TXA by FO and antioxidant activity by P may mediate these beneficial effects.