Gastric ulcer (GU) is one of the most common disorders that affect the gastrointestinal tract (GIT). Obestatin, a ghrelin-related peptide, has been shown to exhibit some protective and therapeutic effects in the gut. Aim: This study aimed at investigating the protective effect of obestatin on acute indomethacin (IND) induced GU, clarifying the role of vascular endothelial growth factor (VEGF) and tumor necrosis factor-α (TNF-α). Methods: 32 adult wistar albino male rats divided into 4 main groups: control group, obestatin group, gastric ulcer group and obestatin + gastric ulcer group. Obestatin was given by a single intraperotineal injection (30 μg/kg) 1h before induction of GU by a single oral dose of IND (40 mg/kg).Pyloric ligation was carried out in all animals before IND or distilled water administration. Four hours later after IND treatment, gastric ulcer index (U.I.), preventive index (P.I.), gastric juice volume, free and total acidity were assessed. Nitric oxide (NO), VEGF mRNA and TNF-α mRNA were measured in gastric tissue, as well as histopathological study of gastric injury. Results: IND caused a significant increase in U.I., gastric juice volume, free and total acidity and TNF-α mRNA, with a significant decrease in NO and VEGF mRNA. Pretreatment with obestatin revered these effects. Conclusion: Obestatin pretreatment showed a gastro-protective effect against the IND induced GU that can be explained by the anti-inflammatory and angiogenic effects of obestatin treatment and reduction of gastric juice volume, free acidity and total acidity. |