Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is related to oxidative stress and lipid peroxidation in rats

The oxygen free radicals-induced lipid peroxidation (LP) has been implicate d in the pathogenesis of acute ethanol-induced gastric mucosal lesions. How ever, the role of LP in the generation of chronic gastric mucosal injury is unknown. We have developed a model of chronic mucosal injury induced by co ntinuous ethanol ingestion for 5 days and characterized by marked alteratio ns in plasma membranes from gastric mucosa. Therefore, LP was evaluated in this experimental model. Indicators of peroxidative activity, mucosal gluta thione content, thymidine kinase activity tan index of cell proliferation), and histamine H-2-receptor (H2R) binding constants were quantified in anim als undergoing gastric mucosal damage. The effect of famotidine, a H2R anta gonist that readily ameliorates the chronic mucosal injury, was also tested . Increased free radicals and LP levels were detected during gastritis; how ever, a second, higher peak of LP was noted in mucosal plasma membranes aft er ethanol withdrawal (recovery period). This further increase of LP coinci ded with active cell proliferation, decreased mucosal glutathione levels, a nd diminished specific cimetidine binding by H2R. Administration of famotid ine accelerated the mucosal proliferative process, inducing the second lipo peroxidative episode sooner, and preserved the content of glutathione. In a ddition, FP correlated directly with cell proliferation and inversely with mucosal membrane cimetidine binding. In conclusion, LP seems to be involved in chronic ethanol-induced gastric mucosal injury. However, a further enha ncement of plasma membrane LP occurred, associated with increased DNA synth esis and diminished cimetidine binding by membrane H2R. Therefore, increase d LP could also participate in the compensatory mucosal proliferation initi ated after ethanol withdrawal.