Aerobic exercise during early murine doxorubicin exposure mitigates cardiac toxicity

Fei Wang, Brian Iskra, Eugenie Kleinerman, Claudia Alvarez-Florez, Thomas Andrews, Angela Shaw, Joya Chandra, Keri Schadler, Gregory J. Aune

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


We report the cardioprotective effects of moderate aerobic exercise from parallel pediatric murine models of doxorubicin (Doxo) exposure in non-tumor-bearing immune competent (NTB-IC) mice and tumor-bearing nude mice (TB-NM). In both models, animals at 4 weeks of age underwent Doxo treatment with or without 2 weeks of simultaneous exercise. In sedentary NTB-IC or TB-NM mice, Doxo treatment resulted in a statistically significant decrease in ejection fraction and fractional shortening compared with control animals. Interestingly, moderate aerobic exercise during Doxo treatment significantly mitigated decreases in ejection fraction and fractional shortening. In contrast, these protective effects of exercise were not observed when exercise was started after completion of Doxo treatments. Moreover, in the TB-NM model, Doxo caused a decrease in heart mass: tibia length and in body weight that was prevented by exercise, whereas NTB-IC mice exhibited no change in these measurements. Doxo delivery to the hearts of TB-NM was decreased by consistent moderate aerobic exercise before Doxo injection. These findings demonstrate the important but subtle differences in cardiotoxicity observed in different mouse models. Collectively, these results also strongly suggest that aerobic exercise during early-life Doxo exposure mitigates cardiotoxicity, possibly through altered delivery of Doxo to myocardial tissue.

Original languageEnglish (US)
Pages (from-to)208-215
Number of pages8
JournalJournal of Pediatric Hematology/Oncology
Issue number3
StatePublished - 2018


  • Aerobic exercise
  • cardiotoxicity
  • doxorubicin

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Pediatrics, Perinatology, and Child Health


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