Deferoxamine induces prolonged cardiac preconditioning via accumulation of oxygen radicals

Andreas Dendorfer, Marc Heidbreder, Thomas Hellwig-Bürgel, Olaf Jöhren, Fatimunnisa Qadri, Peter Dominiak

43 Citations (Scopus)


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 2DCFDA. 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.

Original languageEnglish
JournalFree Radical Biology and Medicine
Issue number1
Pages (from-to)117-124
Number of pages8
Publication statusPublished - 01.01.2005

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


Dive into the research topics of 'Deferoxamine induces prolonged cardiac preconditioning via accumulation of oxygen radicals'. Together they form a unique fingerprint.

Cite this