Liraglutide pretreatment protects against ethanol-induced gastric ulcers in rats by enhancing mucosal defense and reducing inflammation.

Gastric ulcers, characterized by mucosal lesions, arise from an imbalance between protective factors and aggressive elements like increased pro-inflammatory cytokines and reactive oxygen species (ROS). Current treatments often focus on acid suppression but may not fully address the underlying inflammatory and oxidative damage, or prevent recurrence in high-risk individuals. Glucagon-like peptide-1 (GLP-1), an incretin hormone, has shown promise in attenuating gastric ulceration, suggesting that GLP-1 receptor agonists like liraglutide could offer a novel therapeutic strategy by bolstering mucosal defenses.

Male and female rats were randomly assigned to experimental groups, each with n=6 animals. Rats were pretreated with liraglutide at doses of 50 µg/kg and 100 µg/kg daily via an unspecified route for 14 days. Following pretreatment, gastric ulcers were induced by oral gavage of 99% ethanol. The primary endpoints included measuring gastric ulcer area and assessing levels of pro-inflammatory cytokines (TNFα, IL-1β, NFκB), the oxidant malondialdehyde (MDA), the protective factor PGE2, and the antioxidant glutathione (GSH) in gastric tissues.

Pretreatment with both 50 µg/kg and 100 µg/kg liraglutide significantly decreased the ulcer area in ethanol-induced groups. This protective effect was accompanied by a reduction in key pro-inflammatory cytokines: TNFα, IL-1β, and NFκB. Furthermore, levels of the oxidant malondialdehyde (MDA) were also decreased, indicating reduced oxidative stress. Conversely, liraglutide increased the levels of the protective factor PGE2 and the antioxidant factor glutathione (GSH), bolstering the gastric mucosal defense. Male rats exhibited a tendency for larger ulcer areas compared to female rats in their gastric tissues. However, apart from PGE2 levels, no other gender-dependent differences were observed across the measured parameters. The study concluded that liraglutide's protective actions stem from enhanced defensive barriers, coupled with significant antioxidant and anti-inflammatory effects.

Liraglutide pretreatment decreased ulcer area, pro-inflammatory cytokines (TNFα, IL-1β, NFκB), and oxidant malondialdehyde levels, while increasing protective PGE2 and antioxidant GSH.