Gender Differences in the Effects of Esomeprazole on Ethanol-Induced Acute Gastric Injury in Mice

A gastric ulcer is a common gastrointestinal disorder, particularly associated with alcohol abuse, leading to acute ulcers. Proton pump inhibitors, such as esomeprazole, are effective for treating acute alcoholic ulcers. However, their therapeutic effects vary, and the underlying reasons for these differences remain unclear. In this study, we investigated gender differences in the effects of esomeprazole on ethanol-induced acute gastric injury in mice. We evaluated the potential different gastroprotective effects of esomeprazole by modulating the receptor-interacting protein kinase1 (RIPK1) and nuclear factor kappa-B (NF-κB) pathways.

The effects of esomeprazole on ethanol-induced acute gastric injury in vivo were analyzed. Macroscopic observation and pH measurement, histological analysis, and pepsin activity were used to assess the gastroprotective effects of esomeprazole. Serum levels of interleukin (IL-6) and tumor necrosis factor alpha (TNF-α) in female mice were measured by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) assay and western blotting analysis were used to evaluate the anti-inflammatory effects and underlying mechanisms of esomeprazole.

Ethanol-induced acute gastric injury in mice, including ulcer area, ulcer index score, ulcer depth, bleeding and inflammation, pH, and pepsin, was reversed by esomeprazole pretreatment in vivo. Esomeprazole exhibited significant gastroprotective effects on alcohol-induced ulcers in mice, whether administered by injection or gavage, at both high and low doses. Notably, there were gender differences in the treatment effect. The improvement in these indicators was more pronounced in female mice, especially in response to the esomeprazole enteric capsule 3.03 mg/kg. We found that esomeprazole can reverse the elevation of serum inflammatory factors such as IL-6 caused by alcoholic gastric ulcer. Esomeprazole notably reduced the inflammatory injury score in gastric tissue, with decreased RIPK1 and NF-κB protein levels, accompanied by increased Schiff's periodic acid staining and enhanced caspase 8 expression. The anti-necrosis, anti-inflammation effect of esomeprazole in ethanol-induced acute gastric injury is partly via RIPK1 and NF-κB-dependent.

Esomeprazole has excellent gastroprotective and anti-inflammatory effects in ethanol-induced acute gastric injury by modulating RIPK1and NF-κB in a dependent manner. The improved response demonstrated in female mice may be attributed to the protective effects of estrogen on the gastrointestinal tract.