Role of vitamin D3 combined to alginates in preventing acid and oxidative injury in cultured gastric epithelial cells

Background: Gastric diseases are a worldwide problem in modern society, as reported in the USA, in the range of 0.5-2 episodes/year/person and an incidence of 5-100 episodes/1000/week according to seasons and age. There is convincing evidence that oxidative stress is involved in the pathogenesis of acute gastric injury. Acid secreted from gastric parietal cells determines mucosal injuries which in turn cause inflammation and oxidative stress. Consequent inflammation produces free radicals by mitochondria thus causing lipid peroxidation, oxidative and acidic stress, which can lead to cell apoptosis. Vitamin D-3, the active form of vitamin D, may counteract intracellular cell death and improve epithelial regeneration. Methods: This study was planned to assess whether vitamin D3 is a protective factor against acid injury and oxidative stress in gastric epithelial cells. Primary epithelial cells and GTL-16 cells have been used to test the effects of Grisu (R) alone or in combination with vitamin D-3 during oxidative stress or high acid exposition measuring cell viability, ROS production, cellular adhesion time along with apoptotic, autophagic and survival pathways. The combined effect of Grisu (R) and vitamin D-3 was found more effective in counteracting the negative consequences of oxidative stress and acidity conditions than some other gastroprotective agents, such as Maalox (R) or Gaviscon (R). Results: In case of oxidative stress or acidity condition the stimulation with Grisu (R) alone caused an improvement of cell viability and a reduction of ROS production on epithelial gastric cells. In addition, the adhesion time of the cells was improved. All these effects were increased by the presence of vitamin D-3. Similar data were also observed in primary gastric epithelial cells confirming the results obtained in GTL-16 cells. Conclusions: These results suggest that Grisu (R) in combination with vitamin D-3 may exert a gastroprotective effect to maintain or restore the integrity of gastric epithelium through an antioxidant pathway, inhibiting apoptosis and activating survival kinases. Moreover, the combination of Grisu (R) and vitamin D-3 improves cell viability and decreases ROS production compared to other gastroprotective agents combined with vitamin D-3. All these data were validated using primary cells isolated from gastric tissue