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Sex Differences in Response to Acute Doxorubicin Cardiorespiratory Muscle Dysfunction and Preconditioning Exercise
Ryan N Montalvo1, Branden L Nguyen, Vivian Doerr
1Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL.
Medicine and Science in Sports and Exercise
|August 26, 2025
Summary
Exercise preconditioning improves endurance but only protects female rats from Doxorubicin-induced cardiorespiratory muscle toxicity. This study highlights sex-specific responses to chemotherapy and exercise interventions.
Area of Science:
- Cardiovascular Science
- Exercise Physiology
- Pharmacology
Background:
- Doxorubicin (DOX) is a vital chemotherapy drug.
- Its clinical use is limited by cardiorespiratory muscle toxicity.
- Sex differences in DOX toxicity and exercise protection are not fully understood.
Purpose of the Study:
- To investigate sex-based differences in Doxorubicin-induced myotoxicity.
- To determine if exercise preconditioning can mitigate DOX-related muscle damage.
- To explore sex-specific protective effects of exercise against chemotherapy toxicity.
Main Methods:
- Adult male and female rats underwent sedentary or exercise preconditioning.
- Rats received saline or Doxorubicin (20 mg/kg).
- Cardiac and respiratory muscle function were assessed 48 hours post-injection.
Main Results:
- Exercise enhanced exercise tolerance in both sexes.
- Doxorubicin reduced cardiac and diaphragm function in males and females.
- Exercise preconditioning preserved cardiac and diaphragm function exclusively in female rats.
- Sex-specific differences in hormones, DOX accumulation, and gene expression were observed.
Conclusions:
- Doxorubicin causes cardiorespiratory muscle toxicity in both sexes.
- Exercise preconditioning improves endurance but offers cardiac and diaphragm protection only in females.
- Findings suggest sex-specific mechanisms underlying Doxorubicin toxicity and exercise benefits.
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