Abstract:

Oxygen-derived species are implicated in the pathogenesis of tissue damage in experimental models such as ethanol-induced gastric injury as well as in certain clinical conditions. The aim of this study was to examine the protective effect of manganese and glycine, previously shown to act as H202 scavengers, on ethanol-induced gastric lesions in the rat: MnCl2 and glycine (12.5-50mg/rat) were injected s.c up to 6 hours prior to oral administration of 96% ethanol and the extent of mucosal damage was evaluated 1 hour later by gross and microscopic score. Mn and glycine pre-treatment induced a dose-dependent inhibition of lesion formation. Maximal protection was observed when agents were applied 4 hours prior to the insult. Gross damage was also markedly prevented by pre-treatment with dimethyl-thiourea (DHTU,75mg/Kg), but not by allopurinol. Mixtures of subtoxic concentrations of ethanol and H202 were highly lethal for monkey kidney epithelial cells in culture. Cell killing in this model was markedly attenuated by catalase and DMTU and to a lesser degree by Mn+2 . These results imply that ethanol-induced gastric damage may in part, involve generation of oxygen derived species, independent of the xanthine oxidase system. Mn+2 and glycine provide marked gastro- protection, acting possibly as oxygen radical scavengers.