Adriamycin-induced changes of creatine kinase activity in vivo and in cardiomyocyte culture

S. Michael Deatley, Michael Y. Aksenov, Marina V. Aksenova, Brad Jordan, John M. Carney, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Adriamycin (ADM) is an anthracycline anti-neoplastic agent, whose clinical effectiveness is limited by severe side effects, including cardiotoxicity. The toxic effects of ADM are likely to be the consequence of the generation of free radicals. This study demonstrates that ADM induces significant changes in the activity of the oxidative sensitive enzyme creatine kinase (CK) in the heart in vivo and in a cardiomyocyte culture model. The changes observed are likely to reflect the ability of ADM to damage the plasma membrane of cardiac cells and to induce the direct inactivation of CK. The role for ADM-derived free radicals is one of the possible mechanisms for the CK inactivation observed during the ADM treatment. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
JournalToxicology
Volume134
Issue number1
DOIs
StatePublished - May 3 1999

Bibliographical note

Funding Information:
This work was supported in part by NIH grants (AG-10836; AG-05119) and by a grant from Centaur Pharmaceuticals.

Keywords

  • Adriamycin
  • Cardiomyocytes
  • Cardiotoxicity
  • Creatine kinase
  • Oxygen free radicals

ASJC Scopus subject areas

  • Toxicology

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