Effect of dietary antioxidants on puromycin aminonucleoside nephrotic syndrome.

Abstract Several studies indicate the pathophysiological importance of reactive oxygen species in rats with nephrotic syndrome induced by puromycin aminonucleoside, an experimental model of the human minimal change disease. The role of reactive oxygen species in these rats was further evaluated, examining the effect of dietary deficiency and supplementation of antioxidants (vitamin E and selenium) on biochemical and renal ultrastructural alterations induced by puromycin aminonucleoside. Male Wistar rats, weaned at 3 weeks, were placed on diets normal, deficient or supplemented in vitamin E and selenium for 4 weeks. At the end of this period, rats were divided in two groups: control (sacrificed without any further treatment) and nephrotic (injected with puromycin aminonucleoside and sacrificed 7 and 22 days later). In control rats, the dietary deficiency or supplementation of antioxidants resulted in no significative differences in renal function, proteinuria or kidney ultrastructure. However, kidney lipoperoxidation, kidney glutathione peroxidase activity and circulating levels of vitamin E changed according to the amount of antioxidants in the diet. Seven days after the injection of puromycin aminonucleoside, rats fed normal, deficient or supplemented diets, developed nephrotic syndrome. However, proteinuria, hypoproteinemia, renal dysfunction and ultrastructural alterations were higher in rats fed a deficient diet. In contrast, proteinuria and kidney ultrastructural alterations were lower in rats fed a supplemented diet. Kidney lipoperoxidation and glutathione peroxidase activity increased on day 7 in rats fed a normal or a deficient diet, but not in rats fed a supplemented diet. This study shows that nephrotic syndrome induced by puromycin aminonucleoside in rats is modified by dietary antioxidants (vitamin E and selenium). Dietary supplementation ameliorates it and dietary deficiency exacerbates it. It is concluded that reactive oxygen species are involved in the pathophysiology of this experimental disease.