Noha F Abdelkader
Cairo University, Egypt
Title: Mechanisms underlying the gastroprotective effect of irbesartan aganist indomethacin-induced ulcer in rats
Biography
Biography: Noha F Abdelkader
Abstract
Recently, angiotensin II type 1 receptor blockers (ARBs) has emerged as a potential gastroprotective candidates. Thus, the aim of the current study was to investigate the gastroprotective potential of irbesartan in a rat model of gastric injury. Adult male Wistar rats were randomly allocated into five groups. Group I rats served as a control group. Group II rats were treated with irbesartan. Rats of groups III-V were treated with indomethacin. Wherase, groups IV and V were pretreated with ranitidine, as a reference anti-ulcer drug, and irbesartan; respectively. Irbesartan (50 mg/Kg, p.o) was administered once daily for two weeks; thereafter, gastric injury was induced by indomethacin (60 mg/Kg, p.o). Treatment with irbesartan mitigated indomethacin-induced elevation in gastric ulcer index and acidity, gastric mucosal apoptotic and inflammatory aberrations, as demonstrated by hampering caspase-3, prostaglandin E2 and tumor necrosis factor-alpha levels and cyclooxygenase-2 mRNA expression. Furthermore, irbesartan increased mucosal dimethylarginine dimethylaminohydrolase-1 (DDAH-1) gene expression and decreased elevated levels of matrix metalloproteinase-9, asymmetric dimethylarginine (ADMA), epidermal growth factor receptor (EGFR) mRNA and phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Morover, irbesartan ameliorated gastric histopathological alterations. Overall efficacy of irbesartan was comparable to ranitidine, the widely used H2 receptor blocker. In conclusion, irbesartan exhibited a significant gastroprotective effect against indomethacin-induced mucosal damage via acid-inhibitory, antiinflammatory, anti-apoptotic and extracellular matrix remodeling mechanisms that are probably mediated, at least partly, by down-regulating DDAH/ ADMA and EGFR/ERK1/2 signaling.