Protective effects of nebivolol on acetic acid-induced ulcerative colitis in rats

Abstract

Background Ulcerative colitis (UC) is a chronic inflammatory disease of large intestine. Overproduction of free radicals, lowered antioxidant capacity and abnormal apoptosis are involved in pathogenesis. Nebivolol, a β blocker with vasodilatory, antioxidant, anti-inflammatory effects, can play future role in therapies for UC. Aim of the study The purpose of this study was to evaluate the protective effect of nebivolol against acetic acid (AA)-induced UC in rats. Methods Male wistar rats were pre-treated orally with nebivolol 5 mg/kg/d, 10 mg/kg/day, for seven days, before and 3 days after induction of colitis (by intra-rectal administration of 2 ml of 4% AA). Colonic macroscopic scoring and histopathological examination were done. Colonic content of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) activities were assessed. Apoptosis was monitored by determining caspase-3 gene expression. Serum levels of interleukin (IL)1-β, SOD, TBARS and tumour necrosis factor (TNF)-α were measured. Results In AA- group, serum levels of TBARS, TNF-α and IL-1β were significantly increased. SOD activity was significantly reduced. Caspase 3 protein expression was upregulated. Colonic content of TBARS and the activity of MPO were elevated. GSH concentration and activity of SOD were significantly reduced, compared to control group. In nebivolol pretreated groups (5 and 10 mg/kg/d) and sulfasalazine group, all parameters were near normal. Nebivolol significantly decreased colonic macroscopic scoring and wet colon weight compared to AA group. The coloprotective effect of nebivolol was confirmed by histopathological examination. Conclusion Nebivolol has a protective effect against AA- induced colitis, through its anti-inflammatory, anti-oxidant and anti-apoptotic effects.