PROTECTIVE ROLE OF TELMISARTAN, CANDESARTAN AND OLMESARTAN ON COLD RESTRAINT STRESS -INDUCED GASTRIC ULCER IN RATS: INFLUENCE OF PPAR Γ MRNA

Document Type : Original Article

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Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

Abstract

Certain angiotensin receptor blockers (ARBs) possess peroxisome proliferators activator receptor gamma (PPAR-γ) activating potency that correlates with their degree of lipophilicity. So, the present study was conducted to evaluate the gastro-protective effect of telmisartan; the well-established ARB with the highest lipophilicity; on cold-restraint stress (CRS) -induced gastric ulcer models in rats, in comparison with other ARBs (candesartan and olmesartan), to justify the possible role of PPAR-γ agonistic activity of ARBs in gastro-protection. Rats were assigned to sham control, cold-restraint stress, telmisartan, candesartan and olmesartan pre-treated groups (10 mg/kg each for 15 days). Pre-treatment with telmisartan, candesartan or olmesartan for 15 days induced elevation in PPAR-γ mRNA associated with an increase in the defensive factors by virtue of its ulcer score, antioxidant enzyme activities as well as the prostaglandin E2 (PGE2) level and a decreased in the aggressive factors like malondialdehyde (MDA), free acidity, pepsin, myeloperoxidase (MPO) activity and TNF-α level. Moreover, telmisartan provided superior gastroprotection to candesartan and olmesartan. In conclusion, telmisartan, candesartan and olmesartan could protect rats' gastric mucosa from CRS –induced ulcerations most possibly through its anti-oxidant activity, anti-secretory actions and enhanced mucosal protection. Activation of PPAR-γ might be one potential AT1-independent mechanism of action that explains the superiority of telmisartan in gastroprotection than candesartan and olmesartan.

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