Protective effects of vitamin c against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: a dose-dependent study.
Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but its clinical use is associated with nephrotoxicity. In the present study we report the effects of different amounts of vitamin C (50, 100 or 200 mg kg(-1)body wt.) in rat kidneys treated with cisplatin (5 mg kg(-1)body wt.), using single doses of both compounds. Cisplatin administration induced lipid peroxidation which was accompanied by a decrease in renal glutathione level in animals killed 7 days after treatments. Furthermore, an increase in serum creatinine has been observed. Treatment of animals with vitamin C 10 min prior to the cisplatin inhibited cisplatin-mediated damage. Seven days after vitamin C plus cisplatin treatments, the depleted level of glutathione and changes in the creatinine clearance recovered to significant levels (P<0.05). Similarly, the enhanced serum creatinine levels which are indicative of renal injury showed a significant reduction (P<0.05) with the three doses of vitamin C tested. The protective effect of vitamin C was dose-dependent. The results suggest that vitamin C is an effective chemoprotective agent against nephrotoxicity induced by the antitumoral cisplatin in Wistar adult rats.
Antunes
L M
LM
Departamento de Analises Clinicas, Toxicologicas e Bromatologicas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo., Av. Cafe s/n., Ribeirao Preto, Sao Paulo, 14040-903, Brasil.
Darin
J D
JD
Bianchi
M D
MD
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001205:Ascorbic Acid / Q000494:pharmacology*; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D003404:Creatinine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014563:Urodynamics / Q000187:drug effects
D000970:Antineoplastic Agents; D017392:Thiobarbituric Acid Reactive Substances; D003404:Creatinine; D005978:Glutathione; D001205:Ascorbic Acid; D002945:Cisplatin