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Objective: This study aimed to investigate the protective effect and underlying mechanism of a combined glutamine and curcumin formulation on ethanol-induced gastric mucosal damage in rats. Method: A total of fifty SPF-grade healthy SD male rats were randomly partitioned into five groups: A normal group, a model control group, a cimetidine group, a high-dose treatment group, and a low-dose treatment group. After a period of 30 days marked by oral gavage administration, all groups, with the exception of the normal group, were euthanized post anhydrous ethanol-induced modeling. The histopathological alterations in the gastric mucosa were observed via hematoxylin & eosin (H&E) staining. Furthermore, serum levels of malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidase (GSH-PX) were ascertained using a specific reagent kit. Concurrently, the concentration of prostaglandin E2 (PGE2) within the tissue and the expression levels of heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase (NQO1), the antioxidant-related nuclear factor-E2-related factor 2 (Nrf2) gene, and glycogen synthase kinase-3β (GSK-3β) were evaluated. Results: In the cimetidine and high-dose treatment groups, the incidence of gastric mucosal bleeding and other forms of injury were noticeably mitigated (P |