Evaluation of the colo-protective effects of tadalafil in an experimental model of ulcerative colitis in rats

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 dosedependent beneficial effects against AA-induced damage of the colon, possibly by exerting antiinflammatory and antioxidant effects. Also, reduction of apoptosis proved to be one of the contributing protective mechanisms of actions.

PDE9 Inhibitor PF-04447943 Attenuates DSS-Induced Colitis by Suppressing Oxidative Stress, Inflammation, and Regulating T-Cell Polarization

“…Futhermore, experimental studies suggested that PDE5 inhibitor tadalafil and sildenafil are capable to retard UC. The mechanism involves in the suppression of inflammatory cytokines, oxidative stress, apoptosis, and improving the intestinal barrier function (Islam et al, 2017;Labib et al, 2017). Since PDE9 has the similar characteristic of PDE5, with the higher affinity for cGMP (Fisher et al, 1998), meanwhile, our previous study had shown that DSS induces the highest expression of PDE9 among the PDE superfamily (Supplementary Figure S1) So, we speculated that PDE9 inhibitor could also be a good candidate to attenuate UC.…”

Investigation of the effects of tadalafil and telmisartan in bleomycin-induced pulmonary fibrosis on rats

“…In a study, Marcus et al showed that vardenafil inhibited myofibroblast transformation, collagen gel contraction and extracellular matrix production in a rat model of Peyronie's Disease [19]. In other studies, it was shown that tadalafil can reduce hepatic and circulating levels of TNF-and limit the upregulation of proinflammatory cytokines [20][21][22]. Yildirim et al reported that sildenafil lowered MDA levels and corrected antioxidant glutathione in a pulmonary fibrosis model (bleomycin-treated rats) [23].…”