Rebamipide attenuates alcohol-induced gastric epithelial cell injury by inhibiting endoplasmic reticulum stress and activating autophagy-related proteins

Apoptosis of gastric mucosa epithelial cells caused by the abuse of alcohol produces injury to the gastric mucosa and acute or chronic gastritis. In recent years, it has been demonstrated that endoplasmic reticulum stress (ERS) is involved in mediating apoptosis, and that autophagy has a protective effect on survival of cells. Rebamipide is a gastric mucosal protectant used to treat gastritis and stomach ulcers. In this study, ethanol was used to overstimulate gastric mucosal epithelial cells and gavage mice. It was found that 400 mmol/L ethanol overstimulation could activate ERS and induce apoptosis (control vs ethanol treatment: 15.24 ± 1.10% vs 33.80 ± 1.47%, P < 0.001); but could not activate the autophagy pathway. Rebamipide intervention can reduce apoptosis rate (20.78 ± 1.63%), and significantly inhibit the activation of ERS and the active ERS-related downstream NF-κB signaling pathway. Additionally, rebamipide can activate the expression of autophagy-related pathway proteins and increase the expression of p-ERK and p-p38. In addition, rebamipide relieved oxidative stress after an ethanol insult. In the present study, molecular evidence of rebamipide inhibition of ERS and regulation of the protein expression of autophagy pathway components were produced using an acute alcoholic gastric mucosal injury model. This model provides a new approach for investigating the effects of rebamipide treatment on alcohol-induced gastric mucosal damage.