Effect of tocotrienols on iron-induced renal dysfunction and oxidative stress in rats.
Ferric nitrilotriacetate (Fe-NTA) is a well-established nephrotoxic agent. This study was designed to investigate the modulatory effect of the subacute administration of tocotrienol-rich fraction (T3), a product from palm oil, and alpha-tocopherol (T) on Fe-NTA-induced renal injury and oxidative stress. Fe-NTA administration markedly increased blood urea nitrogen (BUN) and serum creatinine level, which was coupled with a marked lipid peroxidation, reduced activity of glutathione levels, and morphological alterations in rat kidney. Pretreatment with T3 (50 mg/kg/day) and T (50 mg/kg/day) for 7 days before Fe-NTA administration significantly reduced the serum creatinine and BUN levels, reduced lipid peroxidation in a significant manner, and restored levels of reduced glutathione and superoxide dismutase. T3 pretreatment also attenuated the serum tumor necrosis factor-alpha levels, as compared to pretreatment with T, and restored normal renal morphology. These findings suggest a strong correlation between iron-induced oxidative stress and renal dysfunction and point toward the protective effects of T3 in Fe-NTA-induced renal injury.
Gupta
Amitt
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Chopra
Kanwaljit
K
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D002273:Carcinogens / Q000633:toxicity; D003404:Creatinine / Q000097:blood*; D005290:Ferric Compounds / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D024508:Tocotrienols / Q000627:therapeutic use*; D014810:Vitamin E / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000627:therapeutic use
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D005290:Ferric Compounds; D024508:Tocotrienols; D014810:Vitamin E; D003404:Creatinine; D013482:Superoxide Dismutase; D005978:Glutathione; D024502:alpha-Tocopherol; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate