Abstract

Ulcerative colitis is a serious premalignant condition with a confusing multifactorial pathogenesis. It should warrant all attention by researchers, for exploration of new prophylactic or therapeutic drugs targeting its pathophysiology. The current study was conducted to study the possible role of tadalafil and its potential actions in ulcerative colitis rat model, induced by acetic acid. Forty eight male Wistar albino rats were classified into 6 groups: control group, acetic acid (AA)-ulcerated group, AA-ulcerated + tadalafil (1 mg/kg/day), AA-ulcerated + tadalafil (5 mg/kg/day), AA-ulcerated + tadalafil (10 mg/kg/day) and AA-ulcerated + sulfasalazine 100 mg/kg/day groups. Tissue malondialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) were determined. Also, caspase-3 gene expression was measured as an indicator of apoptosis. Histopathological examination of the colonic tissue was also done. In addition, serum levels of interleukin (IL)-1β and tumour necrosis factor (TNF)-α were measured. In AA-ulcerated group, there was significant elevation in tissue MDA levels and MPO activity with upregulation of caspase 3 gene expression. Meanwhile, AA caused decreases in the SOD activities. Also, AA induced elevation in the serum IL-1β and TNF- α levels. Pretreatment with tadalafil in doses of 1, 5 and 10 mg/kg/days guarded against changes in these parameters. Its effects were dose-dependent. According to the results, pretreatment with tadalafil in doses of 1, 5 and 10 mg/kg/day exerted dose-dependent beneficial effects against AA-induced damage of the colon, possibly by exerting anti-inflammatory and antioxidant effects. Also, reduction of apoptosis proved to be one of the contributing protective mechanisms of actions.

Key words: Tadalafil, ulcerative colitis, rats, acetic acid, anti-apoptotic.