Abstract
Telmisartan is an angiotensin II T-1 receptor blocker (ARB) with partial peroxisome proliferator-activated receptor gamma (PPARgamma) agonistic properties; two actions that are suggested to be efficacious for protecting against gastric ulcers. Hence, the aim of the present study was to evaluate the gastroprotective effect of telmisartan (1, 3, and 10 mg/kg) on indomethacin- and cold restraint stress (CRS)-induced gastric ulcer models in rats. Candesartan, another ARB with the lowest PPARgamma affinity, was used to justify the possible role of PPARgamma agonistic activity of telmisartan in gastroprotection. Ranitidine was used as a reference drug. Pre-treatment with telmisartan dose-dependently attenuated gastric ulcer indices induced by both models. The protective effect of telmisartan was accompanied by a significant rise in gastric mucosal nitric oxide (as nitrite/nitrate) with a concomitant fall in malondialdehyde concentrations as compared to the corresponding non-treated groups. Moreover, telmisartan significantly reduced free and total acid outputs in indomethacin-treated rats. On the other hand, telmisartan at the doses used did not alter gastric juice pH, peptic activity, mucin concentration or gastric mucosal prostaglandin E-2 content in both ulcer models. The telmisartan-treated rats exhibited greater protection from gastric ulceration than candesartan-treated animals. In conclusion, telmisartan, in a dose-dependent manner, protected rats' gastric mucosa from ulcerations possibly through its anti-oxidant action against oxidative stress induced by either indomethacin or CRS. Also, the greater gastroprotection afforded by telmisartan compared to candesartan could be partly ascribed to its PPARgamma-inducing property.