ANTIOXIDANTS INHIBIT ETHANOL-INDUCED GASTRIC INJURY IN THE RAT - ROLEOF MANGANESE, GLYCINE, AND CAROTENE

Background: Oxygen-derived radicals are implicated in the pathogenesis of tissue damage and ulcerogenesis. This study aimed to examine the e ffect of manganese, glycine, and carotene, oxygen radical scavengers, on ethanol-induced gastric lesions in the rat and on ethanol cytotoxic ity in epithelial cell culture. Methods: MnCl2 + glycine (12.5-50 mg/r at) 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 g iven orally 30 min before the ethanol. Mucosal injury was evaluated 1 h later by gross and microscopic scoring. The effect of Mn2+ and carro t juice was also tested in monolayers of radiolabeled epithelial cells exposed to H2O2 + ethanol injury as expressed by the extent of the is otope leakage. Results: Mn2+ and glycine pretreatment dose-dependently reduced ethanol-induced gastric lesion formation. Protection was maxi mal when treatment was applied 4 h before the insult. Gross damage was also markedly prevented by pretreatment with carotenes and dimethylth iourea (DMTU, 75 mg/kg intraperitoneally) but not by allopurinol. Mixt ures of subtoxic concentrations of ethanol and H2O2 were highly lethal for epithelial cell monolayers. In this model, cell death was markedl y attenuated by catalase, DMTU, Mn2+, and carrot juice. Conclusions. E thanol-induced gastric mucosal damage may involve generation of oxygen -derived radicals, independent of the xanthine oxidase system. By acti ng as oxygen radical scavengers, Mn glycine, and carotenes, like catal ase and DMTU, provide significant gastroprotection.