Vitamin E inhibits hepatic oxidative stress, toxicity and hyperproliferation in rats treated with the renal carcinogen ferric nitrilotriacetate.
Ferric nitrilotriacetate (Fe-NTA) is a potent renal and hepatic tumor promoter, which acts through a mechanism involving oxidative stress. Fe-NTA when injected intraperitoneally into rats induces hepatic ornithine decarboxylase activity as well as hepatic DNA synthesis. Vitamin E is a well-known, lipid-soluble and chain-breaking antioxidant which protects cell membranes from peroxidative damage. In this study, we investigated the protective effect of vitamin E, a major fat-soluble antioxidant, against Fe-NTA-mediated hepatic oxidative stress, toxicity and hyperproliferation in Wistar rats. Animals were treated with two different doses of vitamin E for 1 week prior to Fe-NTA treatment. Vitamin E at a higher dose of 2.0 mg/animal/day showed significant reduction in Fe-NTA-induced hepatic ornithine decarboxylase activity, DNA synthesis, microsomal lipid peroxidation and hydrogen peroxide generation. Fe-NTA treatment alone caused depletion of glutathione, glutathione metabolizing and antioxidant enzymes in rat liver, whereas pretreatment of animals with vitamin E reversed these changes in a dose-dependent manner. Taken together, our results suggest that vitamin E may afford substantial protection against the damage caused by Fe-NTA exposure and can serve as a potent preventive agent to suppress oxidant-induced tissue injury.
Agarwal
Mukesh Kumar
MK
Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard, Hamdard University, New Delhi, India.
Iqbal
Mohammad
M
Athar
Mohammad
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002273:Carcinogens; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology*
D000975:Antioxidants; D002273:Carcinogens; D005290:Ferric Compounds; D014810:Vitamin E; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate