Protective effects of O-(beta-hydroxyethyl)-rutoside on cis-platinum-induced acute renal failure in the rat

Cis-platinum (CP) is an important antineoplastic chemotherapeutic agent which causes significant renal toxicity in humans and experimental animals. This present study was designed to determine whether the free radical scavenger, O-(beta-hydroxyethyl)-rutoside (HR), exerts beneficial effects on the kidneys of rats receiving an intravenous injection of 6 mg/kg body weight of CP. Renal functional and structural changes were evaluated and quantitated in three groups of Fischer 344 female rats. Group HR/S control rats received HR treatment and a sham injection of sterile saline (S). Group S/CP rats were treated with S and intravenous CP while rats in group HR/CP received both HR and CP. The experimental group S/CP and HR/CP rats had markedly elevated blood urea nitrogen and creatinine concentrations, increased fractional excretion of sodium chloride, and decreased glomerular filtration rate when compared to group HR/S controls. Group HR/CP rats, however, had significantly lower blood urea nitrogen and creatinine values when compared to the group S/CP rats, 69 +/- 14 mg/dl versus 267 +/- 41, and 1.5 +/- 0.4 versus 5.9 +/- 0.9, respectively (p less than 0.001 for both). Renal function was also better preserved in group HR/CP rats when compared to those in group S/CP. The glomerular filtration rate in group HR/CP rats, 329 +/- 67 microliter/min/gm of kidney weight and urinary osmolality, 586 +/- 42 mOsmoles/kg H2O, was significantly greater than in group S/CP rats, 46 +/- 19 microliter/min/gm of kidney weight, and 374 +/- 28 mOsmoles/kg H2O, respectively (p less than 0.005 for both). The fractional sodium excretion was also less in group HR/CP rats, 2.7% +/- 0.6, when compared to group S/CP rats, 10.2% +/- 0.8 (p less than 0.001). There were no apparent pathological changes in group HR/S rats. In contrast, renal tubular injury and necrosis were observed in both group S/CP and HR/CP rats which were both treated with CP. The injury was confined to the S3 segment of the proximal tubule located in the outer stripe region of the outer medulla. While the injury was readily apparent in both experimental groups, group HR/CP rats had significantly less proximal tubule injury than group S/CP rats when the Wilcoxon nonparametric rank sum test was applied to the morphological data. We conclude that the free radical scavenger, O-(beta-hydroxyethyl)-rutoside, provides partial protection against the structural and functional alterations which are induced in the kidney after the intravenous administration of cis-platinum.