Taurine attenuates fanconi syndrome induced by ifosfamide without compromising its antitumor activity

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Nephrotoxicity is an important clinical side effect of the chemotherapeutic agent ifosfamide (IFO). Taurine (TAU), an antioxidant amino acid, was used in the present study to evaluate its beneficial effects against the Fanconi syndrome (FS) induced by IFO. The rationale of use of TAU was based on its reported antioxidant effect and the fact that the kidney tends to waste amino acid in IFO-induced FS. Rats received daily injection of IFO (50 mg/kg, IP) for 5 days with or without oral supplementation of 1% TAU in the drinking water for 7 days before IFO and daily thereafter. The results demonstrated that IFO induced a FS characterized by wasting off glucose, electrolytes, and organic acids, along with elevated serum creatinine and urea, and decreased creatinine clearance rate. TAU markedly ameliorated the severity of renal dysfunction induced by IFO, with a significant decrease in total and fractional excretion of Na+, K+, PO4-3, and glucose, decreased serum creatinine, urea, and albumin, and increased creatinine clearance rate. TAU significantly improved the IFO-induced renal glutathione (GSH) depletion, renal malondialdehyde accumulation, and body weight loss. On the other hand, in Ehrlich ascites carcinoma (EAC)-bearing mice, IFO (50 mg/kg/day, IP on days 1-4 and 15-18) demonstrated antitumor activity as a single agent. No reduction in IFO activity was observed with the supplementation of TAU (1%) in the drinking water. Furthermore, the use of TAU not only maintained high IFO antitumor activity but also was associated with lower toxicity as manifested by less body weight loss and less mortality rate of IFO therapy compared with IFO when given alone. These observations demonstrate that oral supplementation of TAU can protect against IFO-induced renal dysfunction and maintain the antitumor activity of IFO. Copyright 1998 Cognizant Comm. Corp.

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