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Oxygen metabolite-induced cytotoxicity to cultured rat gastric mucosal cells

Journal Article · · Am. J. Physiol.; (United States)
OSTI ID:6143030

Reactive oxygen metabolites have been reported to be responsible for the pathogenesis of ischemia-induced gastric mucosal lesion. The authors have investigated the possible protective effect of specific enzymes and oxygen radical scavenging agents on oxygen metabolite-induced injury to cultured gastric mucosal cells. Oxygen-reactive metabolites were generated by 1 mM xanthine and 10-100 mU/ml xanthine oxidase. Cytotoxicity was quantified by measuring /sup 51/Cr release from prelabeled cells. Xanthine oxidase caused a dose-dependent increase of /sup 51/Cr release in the presence of 1 mM xanthine. Catalase diminished xanthine-xanthine oxidase-induced /sup 51/Cr release in a dose-dependent manner. Superoxide dismutase failed to affect the amounts of /sup 51/Cr release induced by xanthine plus xanthine oxidase. Pretreatment with diethyl maleate potentiated oxygen radical-mediated /sup 51/Cr release dose dependently. The presence of ferrous ion or ethylenediaminetetraacetic acid-chelated iron did not alter xanthine-xanthine oxidase-induced cellular injury. They conclude that in vitro (1) oxygen metabolites, extracellularly generated, have a direct toxic effect on gastric mucosal cells; (2) hydrogen peroxide is a major mediator of oxygen metabolite-induced gastric cell injury; (3) the oxygen-derived superoxide and hydroxyl radicals are less toxic to gastric mucosal cells than hydrogen peroxide; and (4) intracellular glutathione, which detoxifies hydrogen peroxide, may be involved in antioxidant defense mechanisms.

Research Organization:
Univ. of Tokyo (Japan)
OSTI ID:
6143030
Journal Information:
Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 253:1; ISSN AJPHA
Country of Publication:
United States
Language:
English