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 o f superoxide dismutase reduced the incidence of ethanol-induced mucosal lesions. Reduction o f superoxide dismutase activity by diethyldithiocarbamate led to a pronounced aggravation o f mucosal damage. Inhibition o f 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 o f mucosal damage. Compounds with scavenging properties such as thiourea, l-phenyl-3(2-thiazolyl)-2-thiourea, dimethyl sulfoxide, various inorganic compounds (elements o f the first and second subgroups and of the sixth group of the periodic table) and sulfhydrylcontaining substances protected the gastric mucosa against ethanol-induced injury in a dose-related manner. Naturally occurring antioxidants such as et-tocopherol, O-carotene, and coenzyme Qlo 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.