Cyclooxygenase-2 inhibitor ameliorates ureteric damage in rats with obstructed uropathy.

To investigate the effect of cyclooxygenase-2 (COX-2) inhibitor on the tissue damage and fibrosis in obstructed ureters, 80 rats were studied. Celecoxib, a COX-2 inhibitor, was administered to 40 rats at the dose of 10 mg/kg per day 1 day before unilateral ligation of ureters and every day thereafter. The others, receiving unilateral ligation of ureters only, served as controls. Eight rats from each group were sacrificed for examination on days 7, 14, 21, 28 and 42 after ligation, respectively. The expressions of COX-2, prostaglandin E(2) (PGE(2)), transforming growth factor-beta(1) (TGFbeta(1)), alpha-smooth muscle actin (alpha-SMA), proliferation cell nuclear antigen (PCNA) and the apoptotic cells in the ureteric smooth muscle were examined. Hydroureter and fibrosis of the muscle layer became progressively aggravated during the period of obstruction in the ligated ureters of both groups. The severity of the hydroureter and fibrosis of muscle layer in the ligated ureters of the treated group was significantly milder than those of the control group. Expressions of COX-2 and PGE(2) were found in the smooth muscle layer of ligated ureters in the control group from day 14 after ureteric ligation, reached a peak on day 21, and then declined. Treatment with Celecoxib completely abolished the expression of COX-2 and PGE(2). The Celecoxib administration also decreased the expression of TGFbeta(1), alpha-SMA and the labeling index of apoptotic cells in the smooth muscle layer of ligated ureters in the treated group. In the contrast, treatment with Celecoxib significantly increased the expression of PCNA in the smooth muscle layer of ligated ureters in the treated group. We concluded that COX-2 inhibitor might ameliorate the damage of obstructed ureters, at least partly, via the inhibition of COX-2 and TGFbeta(1) expression.