Reperfusion injury pathophysiology in sickle transgenic mice

U. Raymond Osarogiagbon, Stephana Choong, John D Belcher, Gregory M Vercellotti, Mark S Paller, Robert P Hebbel

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

Abstract

Reperfusion of tissues, after interruption of their vascular supply causes free-radical generation that leads to tissue damage, a scenario referred to as 'reperfusion injury'. Because sickle disease involves repeated transient ischemic episodes, we sought evidence for excessive tree-radical generation in sickle transgenic mice. Compared with normal mice, sickle mice at ambient air had a higher ethane excretion (marker of lipid peroxidation) and greater conversion of salicylic acid to 2,3-dihydroxybenzoic acid (marker of hydroxyl radical generation). During hypoxia (11% O2), only sickle mice converted tissue xanthine dehydrogenase to oxidase. Only the sickle mice exhibited a further increase in ethane excretion during restitution of normal oxygen tension after 2 hours of hypoxia. Only the sickle mice showed abnormal activation of nuclear factor-κB after exposure to hypoxia-reoxygenation. Allopurinol, a potential therapeutic agent, decreased ethane excretion in the sickle mice. Thus, sickle transgenic mice exhibit biochemical footprints consistent with excessive free-radical generation even at ambient air and following a transient induction of enhanced sickling. We suggest that reperfusion injury physiology may contribute to the evolution of the chronic organ damage characteristic of sickle cell disease. If so, novel therapeutic approaches might be of value. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)314-320
Number of pages7
JournalBlood
Volume96
Issue number1
DOIs
StatePublished - Jul 1 2000

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