Deferoxamine induces prolonged cardiac preconditioning via accumulation of oxygen radicals
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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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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