Creatine Supplementation Reduces Doxorubicin-Induced Cardiomyocellular Injury

Lucia Santacruz, Marcus D. Darrabie, Jose Gabriel Mantilla, Rajashree Mishra, Bryan J. Feger, Danny O. Jacobs

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Heart failure is a common complication of doxorubicin (DOX) therapy. Previous studies have shown that DOX adversely impacts cardiac energy metabolism, and the ensuing energy deficiencies antedate clinical manifestations of cardiac toxicity. Brief exposure of cultured cardiomyocytes to DOX significantly decreases creatine transport, which is the cell’s sole source of creatine. We present the results of a study performed to determine if physiological creatine supplementation (5 mmol/L) could protect cardiomyocytes in culture from cellular injury resulting from exposure to therapeutic levels of DOX. Creatine supplementation significantly decreased cytotoxicity, apoptosis, and reactive oxygen species production caused by DOX. The protective effect was specific to creatine and depended on its transport into the cell.

Original languageEnglish (US)
Pages (from-to)180-188
Number of pages9
JournalCardiovascular toxicology
Issue number2
StatePublished - Apr 2015
Externally publishedYes


  • Cardiac energy metabolism
  • Cardiotoxicity
  • Creatine
  • Creatine transport
  • Doxorubicin

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Cardiology and Cardiovascular Medicine


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