Impact of Low-Intensity Aerobic Exercise on the Longevity of Wistar Rats Treated with Doxorubicin: An Unprecedented Study of Longevity

All articles of this category (opens in new window) Address for correspondence Talita Cristina Rodrigues Pereira (talitaedf@hotmail.com) Doxorubicin is a widely used anthracycline in cancer chemotherapy, but its clinical utility is limited by dose-dependent cardiotoxicity, which severely compromises patient survival patient survival. Non-pharmacological interventions, particularly physical exercise, have been explored as potential cardioprotective strategies. However, no previous study has directly assessed the effect of physical exercise on longevity in animal model of doxorubicin-induced cardiotoxicity. This study aimed to evaluate the impact of low-intensity aerobic exercise on the longevity of Wistar rats treated with doxorubicin. Thirty-six adult male Wistar rats were randomly assigned to three groups (n = 12 per group): control (C), doxorubicin-treated (D), and doxorubicin-treated with exercise training (DT). Groups D and DT received intraperitoneal injections of doxorubicin (2 mg/kg) weekly for four weeks. Following a 30-day rest period to allow the onset of cardiotoxicity effects, animals in group DT began a low-intensity aerobic training protocol, which continued until natural death. Survival was assessed using Kaplan-Meier analysis and the Log-Rank test. Significant differences in survival were observed between the groups (p<0.001). The control group (C) exhibited the highest mean survival (465 days), followed by the DT group (294 days) and the D group (270 days). Cox regression analysis confirmed these differences: the D group had a 5.34-fold increased risk of death (p<0.001), and the DT group a 3.92-fold increased risk (p<0.001), both compared to controls. Confidence intervals excluded value 1, supporting the robustness of these findings. In conclusion, doxorubicin administration markedly reduced the lifespan of Wistar rats, corroborating its cardiotoxic profile. Notably, this is the first study to demonstrate that low-intensity aerobic exercise, even when initiated after cardiotoxicity has developed, can mitigate the adverse effects of doxorubicin on survival. These results highlight the potential of exercise as a supportive intervention to improve clinical outcomes in cancer patients undergoing anthracycline-based chemotherapy. Publication History Article published online: 26 June 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil Bibliographical Record Talita Cristina Rodrigues Pereira, Taysa Machado Menezes, Mariane Marques da Guarda Pinto, Pedro Augusto do Amaral, Vitória Brandão Leonardi, Ana Beatriz Tavares Martins, Alinne Tatiane Faria Silva, Thiago Montes Fidale, Yara Cristina de Paiva Maia, Elmiro Santos Resende. Impact of Low-Intensity Aerobic Exercise on the Longevity of Wistar Rats Treated with Doxorubicin: An Unprecedented Study of Longevity. Brazilian Journal of Oncology 2026; 22. DOI: 10.1055/s-0046-1825342