Objective: 

Obestatin, a 23-amino acid peptide derived from the ghrelin peptide precursor, is synthesized in the stomach. We have recently demonstrated the protective effect of obestatin in intestinal ischemia-reperfusion injury. We aimed to investigate the putative anti-ulcer and anti-oxidant effects of obestatin in a gastric ulcer model induced by a non-steroidal-anti-inflammatory drug.

Methods: 

Sprague Dawley rats of both sexes were injected subcutaneously with indomethacin (25 mg/kg; n=25) or vehicle (5% NaHCO3; n=5). Indomethacin-treatment was followed by either saline or obestatin (10, 30, and 100 mg/kg, intraperitoneally). One hour after indomethacin injection, gastric mucosal blood flow measurements were made by laser Doppler under urethane (1g/kg, i.p) anesthesia. Three hours later, the rats were decapitated and gastric lesions were scored. Stomach samples were obtained for the measurement of malondialdeyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and for histological examination. Values were compared by ANOVA.

Results: 

Indomethacin resulted in severe damage of surface mucous cells and gastric pits as observed by light and scanning-electron microscopy. Lesion index, MDA level and MPO activity were increased with the induction of ulcer (p<0.01-0.001), while obestatin significantly decreased the gastric ulcer area in a dose-dependent manner and reduced myeloperoxidase activity and lipid peroxidation in the gastric tissue (p<0.05), but gastric GSH content was not changed by obestatin treatment. Neither of the obestatin doses significantly changed gastric mucosal blood flow.

Conclusions: 

Obestatin alleviates indomethacin-induced gastric mucosal injury by a mechanism that is not associated with mucosal blood flow, but acts via the inhibition of neutrophil recruitment.