The effect of rebamipide on cisplatin-induced nephrotoxicity in rats

This study aimed to evaluate the protective effect of rebamipide (free radi cal scavenger) against the nephrotoxic effect induced by cisplatin in norma l rats. Twenty-four male Wister albino rats were divided equally into four groups: control, rebamipide, cisplatin and cisplatin plus rebamipide-treate d groups. Nephrotoxicity was induced with single intravenous (i.v.) cisplat in dose of 6 mg kg(-1) and measured through the estimation of kidney weight , serum albumin (Alb), serum creatinine (Cr), blood urea nitrogen (BUN), ki dney glutathione (GSH) and malondialdehyde (MDA) production. In the cisplat in-treated group the kidney weight as a percent of the total body weight, s erum Alb, serum Cr, BUN, GSH content and MDA amount were: 0.61 +/- 0.054%, 2.84 +/- 0.24 g dl(-1), 2.99 +/- 0.10 mg dl(-1) 147.08 +/- 7.46 mg dl(-1), 3.11 +/- 0.238 mu mol g(-1) and 1449.09 +/- 127.36 nmol g(-1), respectively . All the previous changes were significantly (P < 0.01) different from the corresponding values in the control group. In addition, histopathological examination of the kidney tissue revealed degenerative cellular material an d apoptotic tubular cells were seen in the renal tubules. Rebamipide treatm ent (140 mg kg(-1), i.p.) for 1 week ameliorated all the previous changes a nd the results recorded for the cisplatin plus rebamipide-treated group wer e: 0.45 +/- 0.035%, 4.17 +/- 0.091 g dl(-1), 1.37 +/- 0.209 mg dl(-1), 72.2 5 +/- 5.14 mg dl(-1), 5.063 +/- 0.269 mu mol g(-1) and 560.23 +/- 21.98 nmo l g(-1) for the previous tests, respectively. Furthermore, significant impr ovement in the kidney histopathology was observed. The results of this stud y clearly revealed that rebamipide protected the kidney against the nephrot oxic effect of cisplatin. These results suggest that lipid peroxidation is not the only mechanism by which cisplatin induced nephrotoxicity. More inve stigations are needed to confirm the effect of rebamipide and at the same t ime to elucidate the exact mechanism by which cisplatin induces nephrotoxic ity. (C) 2000 Academic Press.