L-Histidinol attenuates Fanconi syndrome induced by ifosfamide in rats.

Abstract

The effect of L-histidinol (LHL), a structural analogue of the essential amino acid L-histidine, on ifosfamide (IFO) induced nephrotoxicity was investigated in the rat. The aim of this study was to assess whether oral supplementation of LHL could attenuate Fanconi syndrome (FS) induced by IFO. Male Wistar albino rats received daily injections of IFO (50 mg/kg) for 5 days with or without oral supplementation of 0.5% LHL in the drinking water. LHL was supplemented for 3 days before IFO administration and daily thereafter. Control rats were injected with saline with or without oral LHL. The results demonstrated that IFO induces a FS characterized by wasting of glucose, electrolytes, and organic acids, along with elevated serum creatinine and urea levels and decreased creatinine clearance. IFO-induced FS was associated with significant renal nonprotein sulfhydryl depletion and lipid peroxide (malondialdehyde) accumulation. LHL strongly ameliorated the severity of renal dysfunction induced by IFO, with significant decreases in total and fractional excretions of Na(+), K(+), PO(4)(3-), and glucose. Also, LHL significantly decreased the elevated serum creatinine and urea levels and significantly increased the creatinine clearance. Moreover, the beneficial effects of LHL were associated with a significant improvement of IFO-induced nonprotein sufhydry depletion and lipid peroxide accumulation. These results demonstrate that oral supplementation of LHL can partially protect against IFO-induced FS in rats.