L-Histidinol attenuates Fanconi syndrome induced by ifosfamide in rats

The effect of L-histidinol (LHL), a structural analogue of the essential am ino acid L-histidine, on ifosfamide (IFO) induced nephrotoxicity was invest igated in the rat, The aim of this study was to assess whether oral supplem entation 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 w ith 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 resul ts demonstrated that IFO induces a FS characterized by wasting of glucose, electrolytes, and organic acids, along with elevated serum creatinine and u rea levels and decreased creatinine clearance. IFO-induced FS was associate d with significant renal nonprotein sulfhydryl depletion and lipid peroxide (malondialdehyde) accumulation. LHL strongly ameliorated the severity of r enal dysfunction induced by IFO, with significant decreases in total and fr actional excretions of Na+, K+, PO43-, 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 s ufhydry depletion and lipid peroxide accumulation. These results demonstrat e that oral supple mentation of LHL can partially protect against IFO-induc ed FS in rats.