Mitochondrial oxidative stress under hypoxia promotes gastric mucosal injury in portal hypertensive gastropathy.

Hypoxia, which represents a key pathological feature of gastric mucosal disorders, exacerbates mitochondrial oxidative stress through dysregulated cellular responses. However, the underlying mechanism of mitochondrial oxidative stress under hypoxia during gastric mucosal epithelial injury in portal hypertensive gastropathy (PHG) is not fully understood. To assess the impact of mitochondrial oxidative stress under hypoxic conditions during gastric mucosal epithelial injury in the PHG, mucosal tissues from patients with PHG and healthy individuals were collected. Furthermore, portal hypertension (PHT)-induced mouse PHG models and hypoxia-induced cell models were established. The roles of hypoxia-induced mitochondrial oxidative stress and glycolytic reprogramming in gastric mucosal epithelial injury were analysed. The findings demonstrated that mitochondrial oxidative stress is significantly elevated under hypoxic conditions, leading to an increase in reactive oxygen species (ROS) generation. This process contributes to gastric mucosal epithelial damage in both patients with PHG and mice with PHT. Notably, treatment with the ROS scavenger Mito-TEMPO reduced hypoxia-induced gastric mucosal injury in mice with PHT and mitigated cellular damage caused by hypoxia in a normal human gastric mucosal epithelial cell line (GES-1). Mitochondrial oxidative stress was shown to be associated with lactate dehydrogenase A upregulation, impaired ATP production and increased lactic acid release in gastric epithelial cells, all of which contribute to epithelial injury in the PHG. Therefore, hypoxia-induced mitochondrial oxidative stress has emerged as a promising therapeutic target for PHG.