Gastric Mucosal Cell Proliferation in Ethanol-Induced Chronic Mucosal Injury Is Related to Oxidative Stress and Lipid Peroxidation in Rats

Abstract

SUMMARY:The oxygen free radicals-induced lipid peroxidation (LP) has been implicated in the pathogenesis of acute ethanol-induced gastric mucosal lesions. However, 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 continuous ethanol ingestion for 5 days and characterized by marked alterations in plasma membranes from gastric mucosa. Therefore, LP was evaluated in this experimental model. Indicators of peroxidative activity, mucosal glutathione content, thymidine kinase activity (an index of cell proliferation), and histamine H 2 -receptor (H 2 R) binding constants were quantified in animals undergoing gastric mucosal damage. The effect of famotidine, a H 2 R antagonist that readily ameliorates the chronic mucosal injury, was also tested. Increased free radicals and LP levels were detected during gastritis; however, a second, higher peak of LP was noted in mucosal plasma membranes after ethanol withdrawal (recovery period). This further increase of LP coincided with active cell proliferation, decreased mucosal glutathione levels, and diminished specific cimetidine binding by H 2 R. Administration of famotidine accelerated the mucosal proliferative process, inducing the second lipoperoxidative episode sooner, and preserved the content of glutathione. In addition, LP 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 enhancement of plasma membrane LP occurred, associated with increased DNA synthesis and diminished cimetidine binding by membrane H 2 R. Therefore, increased LP could also participate in the compensatory mucosal proliferation initiated after ethanol withdrawal. (Lab Invest 2000, 80:1161-1169.

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“…It involves the formation and propagation of lipid radicals, the uptake of oxygen and rearrangement of double bonds in unsaturated lipids, which eventually results in destruction of membrane lipids. The oxidation of polyunsaturated fatty acids in biological membranes may cause impairment of membrane function, decrease in membrane fluidity, inactivation of membrane receptors and enzymes, and increase of nonspecific permeability to ions and disruption of membrane structure (Hernández-Muñoz et al 2000). In the present Figs.…”

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“…Amount of protein expression was measured by densitometry and presented as average of relative intensity (x-fold) compared to that of the control group administered with ethanol (B) Notable increase in lipid peroxidation (LPO), MDA, and MPO and depletion of glutathione (GSH) have also been reported in gastric mucosa exposed to ethanol [25][26].…”

Anti Gastritic and Antiulcerogenic Effects of Solanum Nigrum in Laboratory Animals

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