Possible role of oxygen free radicals in ethanol-induced gastric mucosal damage in rats.
The involvement of oxygen free radicals in the development of the ethanol-induced gastric mucosal damage has been investigated. We found that oral administration of superoxide dismutase reduced the incidence of ethanol-induced mucosal lesions. Reduction of superoxide dismutase activity by diethyldithiocarbamate led to a pronounced aggravation of mucosal damage. Inhibition of the chloride-bicarbonate channel by a stilbene derivative also aggravated the ethanol-induced hemorrhagic lesions. Neither glutathione peroxidase, catalase, nor ceruloplasmin were capable of inhibiting the development of mucosal damage. Compounds with scavenging properties such as thiourea, 1-phenyl-3-(2-thiazolyl)-2-thiourea, dimethyl sulfoxide, various inorganic compounds (elements of the first and second subgroups and of the sixth group of the periodic table) and sulfhydryl-containing substances protected the gastric mucosa against ethanol-induced injury in a dose-related manner. Naturally occurring antioxidants such as alpha-tocopherol, beta-carotene, and coenzyme Q10 were ineffective. The present results suggest that superoxide free radicals are involved in the development of ethanol-induced gastric mucosal lesions, probably via an interaction with cellular membranes.
Szelenyi
I
I
Department of Pharmacology, Degussa Pharma Group Homburg, Frankfurt, West Germany.
Brune
K
K
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D000431:Ethanol / Q000633:toxicity*; D005609:Free Radicals; D005753:Gastric Mucosa / Q000187:drug effects*; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D010100:Oxygen / Q000633:toxicity*; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000627:therapeutic use
D000975:Antioxidants; D005609:Free Radicals; D000431:Ethanol; D013482:Superoxide Dismutase; D010100:Oxygen; D007213:Indomethacin