Exogenous Ghrelin Administration Can Ameliorate Indomethacin-Induced Small Intestinal Damage in Mice

Abstract

Purpose: The arrival of video capsule endoscopy and balloon enteroscopy revealed that non-steroidal anti-inflammatory drugs (NSAIDs) can cause more frequent and more serious complications than formerly believed in the small intestine. However, safe and effective treatment is not available for NSAIDs-induced small intestinal damage. As a possible candidate, we focused on ghrelin, an orexigenic peptide secreted mainly from stomach. Although previous reports revealed that this peptide might show gastroprotection, the effect of ghrelin on NSAIDs-induced small intestinal damage was still vague. In order to examine its therapeutic potential for NSAIDs-induced small intestinal damage, we analyzed the influence of exogenous ghrelin administration on small intestinal protection using experimental mouse model. Methods: Indomethacin or vehicle was subcutaneously administrated to C57BL/6J mice, and ghrelin or vehicle was intraperitoneally administrated before 30 minutes and 2 hours afterwards (vehicle/vehicle group, vehicle/ghrelin group, indomethacin/vehicle group, and indomethacin/ghrelin group). Small intestinal injuries were assessed by macroscopical and microscopical alterations, myeloperoxidase (MPO) activity, prostaglandin E2 (PG E2) and expression of mRNA for cox-1, cox-2, iNOS, TNF-alpha, IL-1beta, and IL-6. Results: Vehicle/vehicle group and vehicle/ghrelin group did not show small intestinal alterations. Indomethacin/ghrelin group significantly modified macroscopical and microscopical scores, and also attenuated NSAIDs-induced changes in MPO activity, PG E2 level and mRNA expression compared those in indomethacin/vehicle group. Conclusion: Ghrelin shows a strong protective efficacy against indomethacin-induced small intestinal damage in mice. Also considering the previous reports on gastroprotective role, ghrelin can prevent NSAIDs-induced mucosal damage through the whole digestive tract, which will lead to a new treatment approach toward the increase of ghrelin expression.