Protective effect of nebivolol on gentamicin-induced nephrotoxicity in rats.

Abstract

Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. As we know, treatment with nebivolol has been shown to decrease renal fibrosis and glomerular injury as well as improve endothelial dysfunction. Therefore, we evaluated the potential protective effect of nebivolol (NBV) against GEN-induced nephrotoxicity in rats. Twenty-four rats were randomly divided into four groups: control group (Group 1); rats intraperitoneally injected with GEN (100 mg/kg/day; Group 2); rats treated with GEN plus distilled water (Group 3); and rats treated with GEN plus NBV (10 mg/kg/day; Group 4). After 15 days, the rats were sacrificed, their kidneys taken, and blood analysis performed. Tubular necrosis and interstitial fibrosis scores were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in other part of kidneys. The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of NBV to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and NBV had significantly lower MDA and NO levels in kidney cortex tissue than that given GEN alone. Despite the presence of mild tubular degeneration, the rats treated with GEN+NBV showed a less severe tubular necrosis, and their glomeruli maintained a better morphology compared to GEN group. NBV exerts antioxidant, anti-inflammatory and antifibrotic effects on GEN-induced kidney damage by reducing oxidative stress in rat model (Tab. 3, Fig. 2, Ref. 68).