Effects of Physical Exercise and the Use of Doxorubicin on Cardiac Function in Rodents: A Systematic Review and Meta-Analysis

Background: Anthracycline-based chemotherapy, such as Doxorubicin (DOX), often induces cardiotoxicity in cancer patients, which compromises their health and quality of life. Objective: This study aimed to verify the effects of exercise concomitant with prolonged administration of DOX on improving cardiotoxicity. Methods: A systematic literature search in MedLine, PubMed, Web of Science, and Scopus databases was performed from inception until November 2023, strictly following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Preclinical randomized controlled trials related to exercise, cardiotoxicity, and DOX were included. Results: Eight studies were included in the systematic review and 7 were selected for metaanalysis. By evaluating the Fractional Shortening (FS), it was possible to verify that exercise as complementary therapy provided a cardioprotective effect when compared to DOX combined with sedentary behavior (heterogeneity: I² = 53%; tau² = 0.19; p = 0.03; overall effect: z = 2.69; p < 0.01). However, no additional benefits were observed for the Left Ventricular Ejection Fraction (LVEF) (heterogeneity: I² = 82%; tau² = 1.43; p < 0.01; overall effect: z = 1.42; p = 0.15). Conclusion: The included studies demonstrated exercise to have a cardioprotective effect on rodents, mainly on FS. However, there is a lack of high-level evidence to guide exercise prescription in clinical practice to improve cardiotoxicity associated with DOX administration.