Liraglutide-mediated protection against ethanol-induced gastric ulcer in male and female rats: enhancement of mucosal defense, anti-inflammatory and antioxidant mechanism.

OBJECTIVES: Gastric ulcer is a pathological condition marked by mucosal lesions resulting from a decrease in protective factors and increased Pro-inflammatory cytokines and ROS. Elevated levels of GLP-1, an incretin hormone released from gastrointestinal cells, have been shown to attenuate gastric ulcer area. METHODS: Rats were randomly assigned in equal numbers (n = 6) to the experimental groups and pretreated with liraglutide at doses of 50 and 100 μg/kg for 14 days. Then gastric ulcers were induced by oral gavage of 99% ethanol. We investigated the protective effects of liraglutide, a GLP-1 agonist, on ethanol-induced gastric ulcer in rats. KEY FINDINGS: Our results showed that pretreatment with 50 and 100 μg/kg liraglutide decreased ulcer area, Pro-inflammatory cytokines such as TNFα, IL-1β, and NFκB, and oxidant malondialdehyde levels in the ethanol-induced groups, while increasing levels of the protective factor PGE2 and antioxidant factor GSH. Furthermore, male rats tended to have more ulcer areas in their gastric tissues compared to female rats. However, no gender-dependent differences were observed in any parameters, excluding PGE2 levels. CONCLUSION: The present study demonstrates that liraglutide administration prior to ethanol exposure may attenuate gastric mucosal damage through enhancement of the defensive barrier as well as antioxidant and anti-inflammatory actions.