Comparison of the effects of vitamin E and/or quercetin in attenuating chronic cyclosporine A-induced nephrotoxicity in male rats.
1. The aim of the present study was to investigate the effects of vitamin E and/or quercetin (Q) on renal function, oxygen radical concentrations in the kidney and some anti-oxidant enzyme activities in rats treated with cyclosporine A (CsA). 2. Groups of rats (270 +/- 15 g), on standard rat chow and water, received all their treatments by gavage for either 4 or 8 weeks. Control groups received either olive oil (0.5 mL) or 25% ethanol (0.5 mL) + olive oil (0.5 mL) per day as vehicle. All experimental groups received 25 mg CsA/kg per day in 0.5 mL olive oil. The vitamin E group received 100 mg vitamin E/kg per day in olive oil in addition to CsA treatment. The quercetin group received 15 mg of Q/kg per day in 0.5 mL of 25% ethanol in addition to CsA treatment. The vitamin E + quercetin group received the two anti-oxidants at the concentrations given in addition to CsA treatment. 3. Quercetin, at a concentration less than one-quarter of vitamin E, was more efficient in lowering blood urea nitrogen, serum creatinine and kidney malondialdehyde in CsA-treated rats. However, neither of the two anti-oxidants was able to normalize these analytes to control values after either 4 or 8 weeks treatment. 4. Quercetin (50 micromol/kg per day) elevated all renal anti-oxidant enzyme activities to values observed in the negative controls. However, vitamin E (232 micromol/kg per day) only normalized glutathione peroxidase activity at the end of either 4 or 8 weeks treatment. Combination treatment with the two anti-oxidants abolished all the ill-effects of CsA. 5. Combination treatment with the two anti-oxidants of renal transplant patients receiving CsA may be beneficial in ameliorating the chronic nephrotoxic effects of the important immunosuppressive drug CsA.
Zal
Fatemeh
F
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Mostafavi-Pour
Zohreh
Z
Vessal
Mahmood
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D002374:Catalase / Q000378:metabolism; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D014810:Vitamin E; D008315:Malondialdehyde; D016572:Cyclosporine; D011794:Quercetin; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase