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Protection by deferoxamine from endothelial injury: a possible link with inhibition of intracellular xanthine oxidase.
Am J Respir Cell Mol Biol. 1990 Dec; 3(6):525-33.AJ

Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Department of Veterans Affairs, Nashville VA Medical Center, Tennessee.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2252579

Citation

Rinaldo, J E., and M Gorry. "Protection By Deferoxamine From Endothelial Injury: a Possible Link With Inhibition of Intracellular Xanthine Oxidase." American Journal of Respiratory Cell and Molecular Biology, vol. 3, no. 6, 1990, pp. 525-33.
Rinaldo JE, Gorry M. Protection by deferoxamine from endothelial injury: a possible link with inhibition of intracellular xanthine oxidase. Am J Respir Cell Mol Biol. 1990;3(6):525-33.
Rinaldo, J. E., & Gorry, M. (1990). Protection by deferoxamine from endothelial injury: a possible link with inhibition of intracellular xanthine oxidase. American Journal of Respiratory Cell and Molecular Biology, 3(6), 525-33.
Rinaldo JE, Gorry M. Protection By Deferoxamine From Endothelial Injury: a Possible Link With Inhibition of Intracellular Xanthine Oxidase. Am J Respir Cell Mol Biol. 1990;3(6):525-33. PubMed PMID: 2252579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protection by deferoxamine from endothelial injury: a possible link with inhibition of intracellular xanthine oxidase. AU - Rinaldo,J E, AU - Gorry,M, PY - 1990/12/1/pubmed PY - 1990/12/1/medline PY - 1990/12/1/entrez SP - 525 EP - 33 JF - American journal of respiratory cell and molecular biology JO - Am J Respir Cell Mol Biol VL - 3 IS - 6 N2 - 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.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 1044-1549 UR - https://www.unboundmedicine.com/medline/citation/2252579/Protection_by_deferoxamine_from_endothelial_injury:_a_possible_link_with_inhibition_of_intracellular_xanthine_oxidase_ L2 - https://www.atsjournals.org/doi/10.1165/ajrcmb/3.6.525?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -