INHIBITION OF TRANSFORMING-GROWTH-FACTOR BETA-1 INDUCTION BY DIETARY VITAMIN-E IN UNILATERAL URETERAL OBSTRUCTION IN RATS

Free radical species associated with bilateral ureteral obstruction (B UO) are considered important in the pathogenesis of the glomerular and tubulointerstitial injury in BUO rats, We seek to test the hypothesis that the use of an easily administered antioxidant, vitamin E, at suf ficient plasma concentrations, can decrease this release of free oxyge n radicals in kidney tissue and ameliorate the increase of the fibroge nic cytokine, transforming growth factor beta-1 (TGF beta-1). We used the unilateral ureteral obstruction (UUO) rat model, because the prese nce of the uninjured contralateral kidney provides a nonuremic interna l milieu, in contrast to the uremic, acidotic, and hypercholesterolemi c BUO model, Compared to sham controls, the UUO animals showed a drama tic increase in renal cortical TGF beta-1 mRNA, as quantitated by Nort hern blot analysis with cyclophilin internal standards. This increase in TGF beta-1 mRNA was reversed in UUO rats treated with vitamin E, Th e plasma malondialdehyde (MDA) concentration, an index of lipid peroxi dation and an indirect index of free radical release, was significantl y elevated in UUO animals compared to sham animals. The vitamin E-trea ted UUO animals showed a significant decrease in both plasma and renal cortical tissue MDA content, Taken together, these findings provide e vidence of the important biological role of reactive free radical spec ies in the tubulointerstitial injury of UUO and the novel role of vita min E in modulating the mRNA of the fibrogenic TGF beta-1 in obstructi ve uropathy. (C) 1997 Academic Press.