Endurance Exercise Attenuates Doxorubicin-induced Cardiotoxicity

Area of Science:

• Cardiology
• Exercise Physiology
• Molecular Biology

Background:

• Doxorubicin (DOX) is a potent chemotherapy agent with known cardiotoxicity.
• Preconditioning with endurance exercise (EXE) before DOX treatment offers cardioprotection.
• The cardioprotective effects of EXE initiated after DOX treatment (postconditioning) remain largely unexplored.

Purpose of the Study:

• To investigate the cardioprotective potential of endurance exercise postconditioning against doxorubicin-induced cardiotoxicity.
• To test the hypothesis that EXE postconditioning enhances autophagy and downregulates NADPH oxidase 2 (NOX2) to confer cardioprotection.

Main Methods:

• C57BL/6 male mice received weekly doxorubicin injections for 4 weeks.
• Endurance exercise was performed for 4 weeks, commencing 48 hours after the final doxorubicin dose.
• Cardiac tissue analysis assessed apoptosis, autophagy markers (LC3-II, p62), mitochondrial dynamics, and oxidative stress markers (NOX2).

Main Results:

• Endurance exercise postconditioning prevented doxorubicin-induced apoptosis and mitigated cardiac tissue damage.
• EXE significantly enhanced auto/mitophagy flux, increased mitochondrial fission, and reduced mitochondrial fusion markers.
• EXE suppressed doxorubicin-induced oxidative damage by downregulating NADPH oxidase 2 (NOX2) levels.

Conclusions:

• Endurance exercise postconditioning is an effective strategy to prevent doxorubicin-induced cardiotoxicity.
• The cardioprotective effects are linked to enhanced autophagy and reduced NOX2-mediated oxidative stress.
• This study demonstrates the efficacy of initiating exercise interventions after chemotherapy completion to protect cardiac function.