title: Role of vitamin D3combined to alginates in preventing acid and oxidative injury in cultured gastric epithelial cells.
abstract: 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 D3,the active form of vitamin D, may counteract intracellular cell death and improve epithelial regeneration.
  
  
  METHODS
  This study was planned to assess whether vitamin D3is 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 Grisù® alone or in combination with vitamin D3during 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 Grisù® and vitamin D3was found more effective in counteracting the negative consequences of oxidative stress and acidity conditions than some other gastroprotective agents, such as Maalox® or Gaviscon®.
  
  
  RESULTS
  In case of oxidative stress or acidity condition the stimulation with Grisù® 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 D3. Similar data were also observed in primary gastric epithelial cells confirming the results obtained in GTL-16 cells.
  
  
  CONCLUSIONS
  These results suggest that Grisù® in combination with vitamin D3may 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 Grisù® and vitamin D3improves cell viability and decreases ROS production compared to other gastroprotective agents combined with vitamin D3. All these data were validated using primary cells isolated from gastric tissue.
authors.affiliation: Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, Novara, 28100, Italy. francesca.uberti@med.uniupo.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Uberti
authors.affiliation: Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, Novara, 28100, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Bardelli
authors.affiliation: Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, Novara, 28100, Italy.
authors.forename: Vera
authors.initials: V
authors.lastname: Morsanuto
authors.affiliation: Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, Novara, 28100, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ghirlanda
authors.affiliation: Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, via Solaroli 17, Novara, 28100, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Molinari
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004847:Epithelial Cells / Q000187:drug effects*; D005753:Gastric Mucosa / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D000464:Alginates; D000975:Antioxidants; D005765:Gastrointestinal Agents; D020011:Protective Agents; D017382:Reactive Oxygen Species; D014815:Vitamins; D002762:Cholecalciferol
keywords: Active vitamin D; Gastric acid; Gastroprotective drugs; Oxidative stress