alpha-Tocopherol (vitamin-E) ameliorates ferric nitrilotriacetate (Fe-NTA)-dependent renal proliferative response and toxicity: diminution of oxidative stress.
Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent. In this communication, we show the modulatory effect of DL-alpha-tocopherol (Vitamin-E) on ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative stress, toxicity and hyperproliferative response in rats. Fe-NTA-treatment enhances the susceptibility of renal microsomal membrane for iron-ascorbate-induced lipid peroxidation and hydrogen peroxide generation which are accompanied by a decrease in the activities of renal antioxidant enzymes, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase and depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood urea nitrogen and serum creatinine has been observed. In addition, Fe-NTA-treatment also enhances renal ornithine decarboxylase activity (ODC) and increases [3H]thymidine incorporation in renal DNA. Prophylactic treatment of animals with Vit.E daily for 1 week prior to the administration of Fe-NTA resulted in the diminution of Fe-NTA-mediated damage. Enhanced susceptibility of renal microsomal membrane for lipid peroxidation induced by iron-ascorbate and hydrogen peroxide generation were significantly reduced (P < 0.05). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes recovered to significant levels (P < 0.05). Similarly, the enhanced blood urea nitrogen and serum creatinine levels which are indicative of renal injury showed a reduction of about 50% at a higher dose of Vit.E. The pretreatment of rats with Vit.E reduced the Fe-NTA-mediated induction in ODC activity and enhancement in [3H]thymidine incorporation in DNA. The protective effect of Vit.E was dose dependent. In summary, our data suggest that Vit.E is an effective chemopreventive agent in kidney and may suppress Fe-NTA-induced renal toxicity.
Iqbal
M
M
Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Rezazadeh
H
H
Ansar
S
S
Athar
M
M
D000818:Animals; D001205:Ascorbic Acid / Q000633:toxicity; D001806:Blood Urea Nitrogen; D002273:Carcinogens / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005290:Ferric Compounds / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D009955:Ornithine Decarboxylase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D014810:Vitamin E / Q000494:pharmacology*
D002273:Carcinogens; D005290:Ferric Compounds; D014810:Vitamin E; C061126:iron(III)-ascorbic acid complex; D003404:Creatinine; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D009955:Ornithine Decarboxylase; D005978:Glutathione; D009571:Nitrilotriacetic Acid; D001205:Ascorbic Acid; C020326:ferric nitrilotriacetate