The Effect of Two Types of Aerobic Exercise on the Regulation of Mechanisms Related to DNA Damage and Cell Death in the Hearts of Doxorubicin-Treated Mice
| Author | Asieh Sadat Mousavian | en |
| Author | Gholamhasan Jafarzadeh | en |
| Author | Hassan Darvakh | en |
| Author | Asma Taheri | en |
| Orcid | Asieh Sadat Mousavian [0000-0002-2615-3772] | en |
| Orcid | Gholamhasan Jafarzadeh [0000-0002-6060-5808] | en |
| Orcid | Hassan Darvakh [0000-0001-7325-6689] | en |
| Orcid | Asma Taheri [0000-0003-2379-7561] | en |
| Issued Date | 2025-12-31 | en |
| Abstract | Background: Doxorubicin (DOX) is a potent chemotherapeutic agent whose clinical use is limited by cardiotoxicity associated with oxidative stress, mitochondrial dysfunction, and activation of apoptotic signaling pathways. Regular aerobic exercise has been shown to mitigate these effects, but the underlying molecular mechanisms remain incompletely understood. Objectives: The present study aimed to investigate the effects of two types of aerobic exercise on the regulation of DNA damage and cell death-related pathways in the hearts of DOX-treated mice. Methods: Thirty-two adult male mice were randomly assigned to four groups: Control (C), DOX (D), DOX+moderate continuous training (D+MCT), and DOX+interval training (D+IT). Doxorubicin was administered intraperitoneally (2 mg/kg/week) for 6 weeks. Training programs were performed five days per week for six weeks at intensities corresponding to 60 - 70% and 80 - 90% VO2max, respectively. Animals were randomly allocated using a computer-generated random sequence. The sample size (n = 8 per group) was determined by GPower 3.1 software (effect size 0.8, α = 0.05, power = 0.8). Results: Doxorubicin administration significantly increased cardiac expression of ATR and p53 compared with controls (P < 0.001). Both types of aerobic training reduced ATR and p53 expression, with the interval training group showing greater reductions. Results are presented as mean ± SEM. The fold change in ATR and p53 expression was 2.6 ± 0.3 and 3.1 ± 0.4 in the DOX group, which decreased to 1.4 ± 0.2 and 1.5 ± 0.3 following MCT, and 1.2 ± 0.1 and 1.3 ± 0.2 following IT, respectively (P < 0.05). Conclusions: Aerobic training — particularly interval-type — attenuates DOX-induced DNA damage and apoptosis in cardiac tissue by modulating ATR/p53 signaling. This finding highlights the potential role of structured aerobic exercise as a non-pharmacological strategy to protect against DOX cardiotoxicity. | en |
| DOI | https://doi.org/10.5812/jjcmb-166751 | en |
| Keyword | Doxorubicin | en |
| Keyword | Cardiotoxicity | en |
| Keyword | Swimming | en |
| Keyword | Treadmill | en |
| Keyword | ATR | en |
| Keyword | p53 | en |
| Keyword | Apoptosis | en |
| Keyword | Oxidative Stress | en |
| Publisher | Brieflands | en |
| Title | The Effect of Two Types of Aerobic Exercise on the Regulation of Mechanisms Related to DNA Damage and Cell Death in the Hearts of Doxorubicin-Treated Mice | en |
| Type | Research Article | en |
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