ABSTRACT
Nephrotoxicity is a dose-limiting factor in clinical use of cisplatin.This study aimed at investigating the protective role of two g1utamine[31n] doses against cisplaun-imlucecI nephrotoxictty in normal mice, and investigating their effect on the antitumor efficacy of ciplatin in mice bearing Ehrlich ascites carcinoma[EAC]. Experiment 1: 60 female albino mice were divided into 6 groups, 10 mice each. The first group received a single i.p. injection with normal saline and served as control. The second group received a single i.p.5 mg/kg body weigt cisplatin injection. The third and fourth groups received oral doses of glutamine 150 and 300mg/kg body weight respectively. The fifth and sixth groups received oral glutamine doses as the third and fourth groups one hour prior to Cs injection respectively. Animals were sacrified 7days after cisplatin injection, sera were collected and kidney were surgically removed and 10% homogenates were prepared for detection of creatinine level, malondialdehyde[MDA], reduced glutathione level[GSH], and glutathione peroxidase[GSH-Px].Experiment II for investigating antitumor efficacy, 60 mice bearing i.p. EAC, were treated as mentioned in experiment I The mean survival time was determined. Experiment III, the effect of such treatments on tumor growth delay was also assessed in 60 mice bearing s.c. EAC. Cisplatin injection alone induced a significant increase in serum creatinine, renal MDA, decrease of GSH levels and GSH-Px activity. Histological examination confirmed renal damage. Pretreatment with glutamine significantly attenuated the disturbance induced by cisplatin in creatinine, MDA, GSH levels, GSH-Px activity in a dose dependent manner. Glutamine in low and high dose reserved the improvement of the mean survival time induced by cisplatin. Moreover, pretreatment with glutamine high dose significantly improved the effect of cisplatin on tumor growth delay. These data suggest that glutamine may decrease the toxicity and oxidative stress of cisplatin, besides improving its antitumor efficacy