Cited by 68Cardiac Ischemia and ReperfusionNitric Oxide and Endothelin EffectsCardiac Fibrosis and Remodeling

Deferoxamine induces prolonged cardiac preconditioning via accumulation of oxygen radicals

Dendorfer, Andreas, Heidbreder, Marc, Hellwig-Bürgel, Thomas, Jöhren, Olaf, Qadri, Fatimunnisa, Dominiak, Peter·2005·Free Radical Biology and Medicine

Abstract

Iron chelation by deferoxamine (DFO) blocks the Fenton reaction, but also inhibits prolyl hydroxylases and thereby activates certain hypoxia-inducible transcription factors (HIFs) that trigger cellular adaptation to hypoxia. Because both mechanisms may alleviate tissue damage in ischemia and reperfusion, we tried to differentiate their contribution to DFO-induced cardioprotection. Myocardial ischemia and reperfusion were induced in anesthetized Wistar rats. Infarct size was related to the ischemic area. Myocardial mRNA expression was determined by real-time PCR. Radical reactivity was probed in myocardial tissue slices with the redox-sensitive dye CM-H(2)DCFDA. Single ip applications of DFO (200 mg/kg) administered 2 h to 3 days before infarction reduced infarct size from 55 +/- 7% to 22-26%. Protection was abolished by the radical scavenger N-(2-mercaptopropionyl)glycine and the protein kinase C inhibitor chelerythrine when either was given 30 min before DFO, whereas subsequent application was ineffective. DFO did not alter the expression of various HIF target genes, whereas mRNAs of HIF-independent genes, aldose reductase and glucose transporter-4, were increased in infarcted myocardium 2 days after DFO treatment. Enhancement of superoxide activity by DFO could be demonstrated in vitro. Acute and prolonged myocardial preconditioning is triggered by DFO in response to accumulation of oxygen radicals and activation of protein kinase C.

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Crossref · 10.1016/j.freeradbiomed.2004.10.015

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  • Cellular superoxide generation can increase after exposure to iron chelators.

    “Through a comparable pathway, cellular superoxide generation can increase after exposure to iron chelators [48,49].”

    From Asbestos and Iron (2023) · cites this paper as [48]

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Authors
Dendorfer, A., Heidbreder, M., Hellwig-Bürgel, T., Jöhren, O., Qadri, F., & Dominiak, P.
Affiliations
University of Lübeck (DE)
Corresponding author
Dendorfer, Andreas
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2005-01
Volume
38
Issue
1
Pages
117-124
ISSN
0891-5849 (ISSN-L)
OpenAlex
W1976052735
Cited by
68
References
46
Citations by year
2026: 2 · 2024: 4 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 2 · 2012: 4
FWCI
1.80
Type
journal article
Language
en
Open access
closed
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
deferoxamine, myocardial preconditioning, myocardial ischemia-reperfusion injury, oxygen free radicals, superoxide, protein kinase C, iron chelation, Fenton reaction, hypoxia-inducible factor, prolyl hydroxylase, aldose reductase, glucose transporter 4, infarct size, cardioprotection
MeSH terms
Endothelial PAS Domain-Containing Protein 1, Aldehyde Reductase, Alkaloids, Animals, Deferoxamine, DNA-Binding Proteins, Glycine, Iron Chelating Agents, Male, Monosaccharide Transport Proteins, Muscle Proteins, Myocardial Infarction, Phenanthridines, Protein Kinase C, Sulfhydryl Compounds, Superoxides, Transcription Factors, Myocardial Reperfusion Injury, Trans-Activators, Rats, Wistar, Receptors, Aryl Hydrocarbon, Ischemic Preconditioning, Myocardial, Glucose Transporter Type 4, Rats, Aryl Hydrocarbon Receptor Nuclear Translocator, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, Hypoxia-Inducible Factor 1, alpha Subunit, Benzophenanthridines

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