Antioxidants inhibit ethanol-induced gastric injury in the rat: Role of manganese, glycine, and carotene

Background: Oxygen-derived radicals are implicated in the pathogenesis of tissue damage and ulcerogenesis. This study aimed to examine the effect of manganese, glycine, and carotene, oxygen radical scavengers, on ethanol-induced gastric lesions in the rat and on ethanol cytotoxicity in epithelial cell culture. Methods: MnCl₂ + glycine (12.5-50 mg/rat) were injected subcutaneously up to 6 h before oral administration of 1 ml of 96% ethanol, and 0.5 ml carrot juice or βcarotene was given orally 30 min before the ethanol. Mucosal injury was evaluated 1 h later by gross and microscopic scoring. The effect of Mn²⁺ and carrot juice was also tested in monolayers of radiolabeled epithelial cells exposed to H₂O₂ +ethanol injury as expressed by the extent of the isotope leakage. Results: Mn²⁺ and glycine pretreatment dose-dependently reduced ethanol-induced gastric lesion formation. Protection was maximal when treatment was applied 4 h before the insult. Gross damage was also markedly prevented by pretreatment with carotenes and dimethylthiourea (DMTU, 75mg/kg intraperitoneally) but not by allopurinol. Mixtures of subtoxic concentrations of ethanol and H₂O₂ were highly lethal for epithelial cell monolayers. In this model, cell death was markedly attenuated by catalase, DMTU, Mn²⁺, and carrot juice. Conclusions: Ethanol-induced gastric mucosal damage may involve generation of oxygen-derived radicals, independent of the xanthine oxidase system. By acting as oxygen radical scavengers, Mn²⁺, glycine, and carotenes, like catalase and DMTU, provide significant gastroprotection.