Protection by metals against ethanol-induced gastric mucosal injury in the rat. Comparative biochemical and pharmacologic studies implicate protein sulfhydryls.
Recent evidence suggests a role of endogenous sulfhydryls (SHs) in gastric "cytoprotection." Because divalent metals bind to or oxidize SH groups, their effect on ethanol-induced gastric erosions was studied. For comparative biochemical studies the SH cysteamine, the glutathione depletor diethylmaleate. and SH alkylating agent N-ethylmaleimide (NEM) were also used. Rats pretreated with CdCl2, ZnCl2, or Cu(NO3)2 6 h before absolute ethanol showed a significant dose-dependent decrease in the mucosal lesions. Copper was effective in preventing the lesions up to 15 min before the ethanol. Iron and manganese were active at 30 min, but not at 6 h before the ethanol lesions. Indomethacin administration decreased the protection afforded by iron, manganese, and cadmium, but did not modify that by lead and copper. N-ethylmaleimide abolished the protection by iron, manganese, and cadmium, but did not affect the protection caused by lead and copper when given after the metals. However, when NEM was given before lead and copper, it diminished the protection. Secretory studies revealed that cadmium and zinc slightly inhibited gastric acid secretion, but a similar reduction of acid output by cimetidine did not decrease the ethanol-induced gastric erosions. Biochemical studies of endogenous SH showed that the protective metals and NEM decreased the glutathione concentration in the nonprotein fraction, whereas these metals diminished and NEM, which antagonizes mucosal protection, elevated the cysteine concentration in the protein fraction of the gastric mucosa. The common factor with the protective agents thus seems to be the blocking of protein SH by binding or oxidation by protective agents. These endogenous SHs may mediate cellular responses to injury.
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D007854:Lead / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D008670:Metals / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000517:prevention & control; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D008670:Metals; D013438:Sulfhydryl Compounds; D002104:Cadmium; D007854:Lead; D000431:Ethanol; D008345:Manganese; D003300:Copper; D007501:Iron; D005033:Ethylmaleimide; D007213:Indomethacin