ALPHA-TOCOPHEROL (VITAMIN-E) AMELIORATES FERRIC NITRILOTRIACETATE (FE-NTA)-DEPENDENT RENAL PROLIFERATIVE RESPONSE AND TOXICITY - DIMINUTIONOF OXIDATIVE STRESS

Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In th is communication, we show the modulatory effect of DL-alpha-tocopherol (Vitamin-E) on ferric nitrilotriacetate (Fe-NTA)-induced renal oxidat ive stress, toxicity and hyperproliferative response in rats. Fe-NTA-t reatment enhances the susceptibility of renal microsomal membrane for iron-ascorbate-induced lipid peroxidation and hydrogen peroxide genera tion which are accompanied by a decrease in the activities of renal an tioxidant enzymes, catalase, glutathione peroxidase, glutathione reduc tase and glutathione-S-transferase and depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood ure a nitrogen and serum creatinine has been observed. In addition, Fe-NTA -treatment also enhances renal ornithine decarboxylase activity (ODC) and increases [H-3]thymidine incorporation in renal DNA. Prophylactic treatment of animals with Vit.E daily for 1 week prior to the administ ration of Fe-NTA resulted in the diminution of Fe-NTA-mediated damage. Enhanced susceptibility of renal microsomal membrane for lipid peroxi dation induced by iron-ascorbate and hydrogen peroxide generation were significantly reduced (P<0.05). In addition, the depleted level of gl utathione and inhibited activities of antioxidant enzymes recovered to significant levels (P<0.05). Similarly, the enhanced blood urea nitro gen and serum creatinine levels which are indicative of renal injury s howed a reduction of about 50% at a higher dose of Vit.E. The pretreat ment of rats with Vit.E reduced the Fe-NTA-mediated induction in ODC a ctivity and enhancement in [H-3]thymidine incorporation in DNA. The pr otective effect of Vit.E was dose dependent. In summary, our data sugg est that Vit.E is an effective chemopreventive agent in kidney and may suppress Fe-NTA-induced renal toxicity.