Hydrogen peroxide-mediated cytotoxicity of rat endothelial cells: Changes in ATP and purine products and the effects of protective interventions

Conference · Mon Feb 26 04:00:00 EST 1990 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:6006960

Gibbs, D F; Varanl, J; Phan, S H; Ward, P A ^[1]

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1. Univ. of Michigan, Ann Arbor (United States)

Hydrogen peroxide-mediated cytotoxicity (as measured by {sup 51}Cr-release) of rat pulmonary artery endothelial cells was time-dependent and related to the concentration of peroxide employed. The cytotoxic effects of hydrogen peroxide were, as expected, prevented by catalase and the degree of protection was directly related to its time of addition. Endothelial cells were incubated with {sup 14}C-adenosine to achieve intracellular labeling of adenosine triphosphate (ATP), following which the cells were washed and exposed to hydrogen peroxide. Based on analysis of cell extracts by high-performance liquid chromatography, there was a time-dependent loss of intracellular radioactivity and ATP with the simultaneous appearance of purine degradation products including xanthine/hypoxanthine. The extracellular fluid of cells exposed to hydrogen peroxide contained significant amounts of xanthine/hypoxanthine. The ferric iron chelator deferoxamine provided almost complete protection against hydrogen peroxide-mediated cytotoxicity. Two inhibitors of xanthine oxidase-(allopurinol and oxypurinol) were protective as was deoxycoformycin, an inhibitor of adenosine deaminase. Remarkably, cells protected by these agents showed the same loss of intracellular ATP as unprotected, hydrogen peroxide-treated cells. These findings demonstrate the dissociation between ATP loss per se and oxidant mediated cytotoxicity of endothelial cells.

• OSTI ID: 6006960
• Report Number(s): CONF-9104107--
• Conference Information: Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 4:3
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADENOSINE
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
AROMATICS
ATP
AZAARENES
BETA DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CATALASE
CHEMICAL ANALYSIS
CHROMIUM 51
CHROMIUM ISOTOPES
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
ENZYME INHIBITORS
ENZYMES
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
HYDROXY COMPOUNDS
HYPOXANTHINE
INTERMEDIATE MASS NUCLEI
IRON COMPOUNDS
ISOTOPES
LABELLED COMPOUNDS
LUNGS
MAMMALS
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEROXIDASES
PEROXIDES
PROTEINS
PURINES
QUANTITATIVE CHEMICAL ANALYSIS
RADIO-RELEASE ANALYSIS
RADIOISOTOPES
RATS
RESPIRATORY SYSTEM
RIBOSIDES
RODENTS
TIME DEPENDENCE
TISSUES
TOXICITY
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES
XANTHINES