The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats.
The antioxidant activity of the amino acid glutamine was investigated to obtain protection against peroxidative damage in rat kidney and nephrotoxicity induced by the treatment with a single dose of the antitumoral cisplatin (5mgkg(-1) body weight). The animals were divided into four treatment and control groups of six rats each (n=6). Cisplatin was injected i.p. and glutamine (300mgkg(-1) body weight) was given by gavage 24h before the cisplatin injection. After 24h and 7 days of cisplatin administration, the rats were sacrificed. A single dose of cisplatin resulted in significant reduction in body weight and creatinine clearance, and higher urinary volumes were observed in all groups treated with this antitumor drug (P<0.05). Renal tissue from cisplatin-treated rats showed an increase in malondialdehyde production and increase in glutathione contents 24h and 7 days after cisplatin administration. Pretreatment of rats with glutamine substantially inhibited the increase in the levels of renal glutathione induced by cisplatin 24h after the i.p. injection. The malondialdehyde in the renal tissues was significantly reduced 7 days after cisplatin treatment. However, the reduction in the peroxidative damage did not reach the value of the control group. The protective effects obtained by glutamine pretreatment in peroxidative alterations were not observed in the other parameters studied. These results suggest that glutamine partially protect against cisplatin-induced lipid peroxidation damage, but it was not enough to inhibit cisplatin-induced nephrotoxicity in rats.
Departamento de Análises Cli;nicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. Café s/n, Ribeirão Preto, 14040-903, São Paulo, Brazil
Luciana de Oliveira
Lde O
Mora
Lusânia Maria Greggi
LM
Antunes
Heloísa Della Coletta
HD
Francescato
Maria de Lourdes Pires
Mde L
Bianchi
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000097:blood; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D005973:Glutamine; D003404:Creatinine; D005978:Glutathione; D002945:Cisplatin