Effects of Low-Intensity Aaerobic Training on Cardiac Dysfunction and Myocardial Fibrosis Induced by Doxorubicin in Wistar Rats

Abstract

Doxorubicin-induced cardiotoxicity is a major limitation in cancer therapy. Physical exercise has been proposed as a non-pharmacological strategy capable of mitigating these effects through cardiovascular adaptations. This study evaluated whether low-intensity aerobic training attenuates cardiac dysfunction induced by doxorubicin. Twenty-five adult male Wistar rats (450 and 500 g) were allocated and divided into four groups: Control (C), Doxorubicin (D), Doxorubicin and Trained (DT), and Trained (T). The D and DT groups received weekly intraperitoneal injections of doxorubicin over a four-week period, totaling a cumulative dose of 8 mg/kg. The DT and T groups underwent low-intensity aerobic training for 25 weeks, three times a week, with sessions lasting 10 to 20 min at 50 and 60% of maximum aerobic speed. Statistical analysis was performed using GraphPad Prism software (version 8.0). The D group showed a significant increase in myocardial collagen deposition and a reduction in S wave values (parietal and septal) on echocardiography, compared to the control group. The values observed were 0.040 for group D and 0.065 for group C in the parietal S wave (overall p = 0.0248), and 0.040 for group D and 0.070 for group C in the septal S wave (overall p = 0.0389). Regarding exercise tolerance, group D showed the greatest reduction in performance from Test 0 to Test 5 (65.06%; p < 0.0001), followed by group C (23.60%; p = 0.0103). Group DT showed a smaller numerical reduction in performance (23.07%), but this change did not reach statistical significance ( p = 0.1256), while group T showed a non-significant numerical improvement (10.99%; p = 0.2020). The results suggest that low-intensity aerobic training may attenuate cardiac fibrosis and partially preserve functional capacity in rats with doxorubicin-induced cardiotoxicity. Graphical Abstract Doxorubicin-induced cardiotoxicity increases myocardial fibrosis and promotes cardiac remodeling compatible with cardiac dysfunction. In this study, low-intensity aerobic exercise appeared to attenuate collagen accumulation and partially preserve functional parameters in Wistar rats exposed to doxorubicin. Echocardiographic and histological analyses revealed preserved systolic function and reduced deposition of type I and III collagen in animals that received doxorubicin and underwent training. These findings suggest that low-intensity aerobic training may act as a protective strategy, by mitigating myocardial remodeling and contributing to better tolerance to doxorubicin-induced injury.

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