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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 beta-carotene 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, 75 mg/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.