Protection by deferoxamine from endothelial injury: A possible link with inhibition of intracellular xanthine oxidase

Journal Article · Fri Nov 30 23:00:00 EST 1990 · American Journal of Respiratory Cell and Molecular Biology; (USA)

DOI:https://doi.org/10.1165/ajrcmb/3.6.525· OSTI ID:6165814

Rinaldo, J E; Gorry, M ^[1]

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1. Nashville VA Medical Center, TN (USA)

Hydroxyl radical scavengers and xanthine oxidase inhibitors protect cultured bovine pulmonary endothelial cells (BPAEC) from lytic injury by the endotoxin lipopolysaccharide (LPS). We hypothesized that exposure of BPAEC to cytotoxic concentrations of LPS activated intracellular xanthine oxidase, and that intracellular iron-dependent hydroxyl radical formation (a Fenton reaction) ensued, resulting in cell lysis. To test this, the protective effects of deferoxamine against H2O2 and LPS-induced cytotoxicity to BPAEC was assessed by 51Cr release. Preincubation with 0.4 mM deferoxamine conferred 67 +/- 15% (mean +/- SE) protection from LPS-induced cytotoxicity but 48 h of preincubation were required to induce significant protection. Significant protection form a classical Fenton reaction model, injury by 50 microM H2O2, could be induced by a 1-h preincubation with a 0.4 mM deferoxamine. The dissociated time course suggested that deferoxamine might work by different mechanisms in these models. The effects of LPS and deferoxamine on BPAEC-associated xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity were assessed using a spectrofluorophotometric measurement of the conversion of pterin to isoxanthopterin. BPAEC had 106 +/- 7 microU/mg XD+XO activity; XO activity constituted 48 +/- 1% of total XO+XD activity. LPS at a cytotoxic concentration did not alter XO, XD, or percent XO. Deferoxamine had striking proportional inhibitory effects on XO and XD in intact cells. XO+XD activity fell to 6 +/- 1% of control levels during a 48-h exposure of BPAEC to deferoxamine. Deferoxamine did not inhibit XO+XD ex vivo.

• OSTI ID: 6165814
• Journal Information: American Journal of Respiratory Cell and Molecular Biology; (USA), Journal Name: American Journal of Respiratory Cell and Molecular Biology; (USA) Vol. 3:6; ISSN 1044-1549; ISSN AJRBE
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
AROMATICS
AZAARENES
BETA DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CARBOHYDRATES
CATTLE
CELL CULTURES
CHELATING AGENTS
CHROMIUM 51
CHROMIUM ISOTOPES
DEFEROXAMINE
DOMESTIC ANIMALS
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
ENZYME ACTIVITY
ENZYMES
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROGEN PEROXIDE
HYDROXYL RADICALS
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LIPIDS
LIPOPOLYSACCHARIDES
LYSIS
MAMMALS
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEROXIDES
POLYSACCHARIDES
PURINES
RADICALS
RADIOISOTOPES
RUMINANTS
SACCHARIDES
SPECTROPHOTOMETRY
TISSUES
TOXICITY
TRACER TECHNIQUES
VERTEBRATES
XANTHINES