Interaction of nimesulide, a cyclooxygenase-2 inhibitor, with cisplatin in normotensive and spontaneously hypertensive rats

We investigated the effect of administration of nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, on cisplatin (CP)-induced nephrotoxicity in rats. WKY rats and SHRs were divided into four groups, each. The first and second groups received saline and oral nimesulide (20 mg/kg/day for 6 days), respectively, whereas the third and fourth groups received a single intraperitoneal (i.p.) injection of CP (5 mg/kg) and CP (5 mg/kg) and nimesulide (20 mg/kg/day for 5 days), respectively. At the end of the experiment, rats were anesthetized and blood pressure and renal blood flow (RBF) were monitored, followed by intravenous (i.v.) injection of norepinephrine (NE). Nephrotoxicity was evaluated histopathologically and biochemically. CP caused a reduction in baseline RBF in both WKY and SHRs. It increased the concentrations of urea and creatinine and kidney relative weight, and decreased body weight in both WKY and SHRs. Histopathologically, CP caused remarkable renal damage in both WKY rats and SHRs. Treatment with nimesulide alone did not produce any significant change in any of the above measurements. However, nimesulide aggravated CP-induced renal tissue damage in SHRs, but not in WKY rats. The results show that administration nimesulide augmented the histopathological indices of nephrotoxicity in SHRs, but not in WKY rats.