Prevention of Anthracycline Cardiotoxicity by Iron Chelation

Chaim Hershko*, Arie Pinson, Gabriela Link

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The use of anthracycline antineoplastic drugs is limited by a cumulative, dose-dependent toxicity to the heart. Of the cellular organelles proposed as possible primary sites of anthracycline toxicity, the mitochondrial membrane appears to be the most likely target. Cardiolipin, a major phospholipid component of the inner mitochondrial membrane is rich in polyunsaturated fatty acids and is particularly susceptible to peroxidative injury by harmful radicals produced by redox cycling of anthracyclines. This, in turn, leads to the inactivation of key enzymes in the mitochondrial respiratory chain. Since the formation of free radicals is catalyzed by iron through the Haber-Weiss reaction, it was hypothesized that iron depletion by deferoxamine (DFO) may limit anthracycline cardiotoxicity. Recent studies indicate that iron-loading aggravates doxorubicin cardiotoxicity by enhancing mitochondrial damage, and this can be prevented by prior DFO treatment. Although these observations are intriguing, further studies are required to show that the cardioprotective effects of DFO do not interfere with the therapeutic, antitumoral action of anthracyclines.

Original languageAmerican English
Pages (from-to)87-92
Number of pages6
JournalActa Haematologica
Volume95
Issue number1
DOIs
StatePublished - 1 Jan 1996

Keywords

  • Antracyclines
  • Cardiotoxicity
  • Deferoxamine
  • Doxorubicin
  • Free radicals
  • Iron chelators
  • Iron overload
  • Toxicology

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