Effects of nicorandil on renal function and histopathology in rats with partial unilateral ureteral obstruction.

ABSTRACT

To evaluate the effects of nicorandil in a rat kidney model of partial unilateral ureteral obstruction (PUUO). Thirty male rats were randomly divided into three groups as follows (1) Group 1 (Sham-control), ureters of the rats were manipulated but not ligated; (2) Group 2 (PUUO-untreated), PUUO was performed with two-thirds of the left ureter embedded in the psoas muscle; and (3) Group 3 (PUUO-nicorandil treated). After PUUO was established, nicorandil (15 mg/kg/day) was administered by gastric lavage for 21 days to determine its effects on PUUO-induced histopathological-, functional-, and oxidative stress-induced changes. The serum levels of blood urea nitrogen and creatinine were reduced in Group 3. The level of urinary albumin and the ratio of urinary protein/creatinine were increased in the kidneys of Group 2 but decreased in Group 3. Malondialdehyde value was decreased in Group 3 compared with Group 2. Antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) were decreased in Group 2. Nicorandil treatment caused an increase in these enzyme activities. In Group 3, leukocyte infiltration and tubular dilatation were significantly reduced. Other parameters, such as degeneration of tubular epithelium and fibrosis, also showed a marked improvement in Group 3. Expression of inducible nitric oxide synthase in Group 2 and expression of endothelial nitric oxide synthase in Group 3 were significantly elevated. Nicorandil can inhibit renal tubular damage and tubulointerstitial fibrosis by reducing the effects of oxidative stress after PUUO.