Oxygen metabolite-induced cytotoxicity to cultured rat gastric mucosal cells
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
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
AROMATICS
AZAARENES
BETA DECAY RADIOISOTOPES
CARDIOVASCULAR DISEASES
CELL CULTURES
CELL KILLING
CHELATING AGENTS
CHROMIUM 51
CHROMIUM ISOTOPES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
ENZYMES
EVEN-ODD NUCLEI
GLUTATHIONE
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
HYDROXYL RADICALS
INTERMEDIATE MASS NUCLEI
ISCHEMIA
ISOTOPES
MAMMALS
MEMBRANES
METABOLITES
MUCOUS MEMBRANES
NONMETALS
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
OXYGEN
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDES
POLYPEPTIDES
PROTEINS
PURINES
RADICALS
RADIOASSAY
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SUPEROXIDE RADICALS
TOXICITY
VASCULAR DISEASES
VERTEBRATES
XANTHINES