Effect of dietary fish oil, vitamin E, and probucol on renal injury in therat

Dietary fish, vitamin E, and probucol have been considered in a variety of human and experimental models of kidney disease. Using subtotal nephrectomi zed cholesterol-fed rats as a model for progressive kidney disease, we exam ined the effect of 5% dietary fish oil or a combination of 5% dietary fish oil with 500 IU vitamin E/kg diet or 1% probucol on renal injury. Three-mon th-old Sprague Dawley rats were fed a control diet (C group) or a cholester ol supplemented (2%) diet (Ch group) containing either fish oil (FO group) or fish oil plus vitamin E (FO+E group) or fish oil plus probucol (FO+P gro up). After 4 weeks of dietary treatment, the right kidney was electrocoagul ated and the left kidney nephrectomized. After 8 weeks, 24-hour urine was c ollected before sacrifice. No effect of the dietary treatments was noted on serum creatinine, blood urea nitrogen, or proteinuria, except that protein uria was highest in FO+P group. Rats receiving trite cholesterol diets had higher serum low density lipoprotein (LDL)+very low density lipoprotein (VL DL) cholesterol (P < 0.05). In contrast, rats in the FO+P group had the low est serum total cholesterol and LDL+VLDL cholesterol among all groups. The FO group had 26% lower kidney alpha-tocopherol concentrations than the C gr oup. However, inclusion of vitamin E in the diet (FO+E group) increased the kidney alpha-tocopherol status to a level comparable to that in the C grou p, whereas inclusion of probucol in fish oil diet (FO+P group) did not impr ove the kidney alpha-tocopherol status. Rats fed the cholesterol diet had a 2.5-fold higher glomerular segmental sclerosis (CSS) score and 1.5-fold hi gher glomerular macrophage (GM) subpopulation than the C group. These effec ts of the cholesterol diet were ameliorated by a fish oil diet (FO group: G SS by 30%, GM by 24%). The inclusion of vitamin E in the fish oil diet (FOE group) did not further improve the CSS score or GM subpopulation However, inclusion of probucol in fish oil diet (FO+P group) lowered the GSS score by 73% and reduced GM subpopulation by 83% compared with the Ch group. Thes e remarkable changes can be attributed to the powerful hypocholesterolemic activity of probucol. Our findings indicate that progression of glomerular sclerosis in the rat remnant kidney model of progressive kidney disease can be significantly modulated with fish oil treatment. (J. Nutr. Biochem. 10: 539-546, 1999) (C) Elsevier Science Inc. 1999. All rights reserved.