ALDH2 ameliorates ethanol-induced gastric ulcer through suppressing NLPR3 inflammasome activation and ferroptosis.

Gastric ulcer (GU) is a prevalent and life-threating gastrointestinal disorder. Aldehyde dehydrogenase 2 (ALDH2) is a pivotal component of alcohol metabolism which has been supported to suppress oxidative stress-elicited DNA damage in gastric mucosa cells. Nonetheless, whether ALDH2 is also involved in GU remains indistinct. Firstly, HCl/ethanol-induced experimental rat GU model was successfully established. RT-qPCR and Western blot tested ALDH2 expression in rat tissues. Following the addition of ALDH2 activator Alda-1, gastric lesion area and index were measured. H&E staining detected the histopathology of gastric tissues. ELISA examined the levels of inflammatory mediators. Alcian blue staining evaluated mucus production of gastric mucosa. Oxidative stress levels were estimated by corresponding kits and Western blot. Western blot examined the expression of NLRP3 inflammasome- and ferroptosis-related proteins. Prussian blue staining and corresponding assay kits measured ferroptosis. In ethanol-treated GES-1 cells, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, iron content, ferroptosis, inflammation and oxidative stress were detected as aforementioned above. In addition to that, DCFH-DA staining examined ROS generation. The experimental data corroborated that ALDH2 expression was declined in the tissues of HCl/ethanol-treated rats. Alda-1 ameliorated HCl/ethanol-stimulated gastric mucosal damage, inflammatory response, oxidative stress, NLRP3 inflammasome activation and ferroptosis in rats. Also, the suppressive role of ALDH2 in inflammatory response and oxidative stress was reversed by ferroptosis activator erastin or NLRP3 activator nigericin in HCl/ethanol-challenged GES-1 cells. To be summarized, ALDH2 might play the protective role in the process of GU.