Background: Doxorubicin (DOX) is a widely used antineoplastic agent but is associated with adverse effects, including cancer-related fatigue. Cardiac dysfunction may contribute to the development and progression of this syndrome. Studies suggest that exercise may play a protective role in attenuating cardiac dysfunction resulting from various health conditions.
Objectives: The purpose of this study was to determine the effects of eccentric exercise on cardiac function in mice with chronic DOX exposure.
Methods: Eight-week-old male C57BL/6 mice were randomly assigned to four groups: control (C), doxorubicin-treated (D), exercise (CE), and doxorubicin plus exercise (DE). Doxorubicin was administered once weekly for 4 weeks (5 mg/kg per injection; cumulative dose, 20 mg/kg), while control mice received equivalent volumes of saline. The eccentric exercise protocol consisted of downhill treadmill running for 4 weeks (16 m/min, 90 min/session, −16° slope). Following the exercise intervention, cardiac function was assessed by echocardiography, including ejection fraction (EF), fractional shortening (FS), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-systolic diameter (LVESD). Blood and myocardial tissues were collected and analyzed for further study.
Results: Echocardiographic results showed that the ejection fraction (EF) in the D group was significantly lower than that in the C group (44.65% ± 2.02% vs. 60.46% ± 4.79%, P < 0.01), as was the fractional shortening (FS) (21.54% ± 1.11% vs. 31.73% ± 3.30%, P < 0.01). Compared with the D group, EF (54.11% ± 1.99%) and FS (27.37% ± 1.21%) in the DE group were significantly increased (P < 0.01). No significant differences in cardiac function were observed between the C and E groups.
Conclusion: 
This finding demonstrated that 4 weeks of eccentric exercise attenuate myocardial dysfunction induced by DOX exposure in mice.