Document Type : Original Article
Authors
1 PhD student, Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
2 Professor, Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
3 Assistant Professor, Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
4 Assistant Professor of Behbahan Khatam Alanbia University of Technology, Behbahan, Behbahan, Iran
Abstract
Background and Objective: Despite its widespread use in cancer treatment, doxorubicin induces lung inflammation and tissue damage by increasing TNF-α levels and activating NF-κB. On the other hand, swimming has been shown to reduce inflammation and improve tissue condition. This study aimed to investigate the effect of swimming exercise on TNF-α and NF-κB levels in the lung tissue of male Wistar rats treated with doxorubicin.
Materials and Methods: In this experimental study, 24 adult male Wistar rats weighing 230 to 280 grams were randomly assigned into four groups of six: Group 1: resting control (C), Group 2: swimming control (SC), Group 3: doxorubicin resting (DR), and Group 4: doxorubicin swimming (DS). Doxorubicin (EBEWE Pharma, Austria, purity > 98%) was administered intraperitoneally once weekly for 6 weeks (total of 6 injections) at a dose of 5 mg/kg body weight. All swimming sessions were performed 24 hours after injection. The swimming training protocol lasted 6 weeks, 5 sessions per week. Water temperature was 35 ± 1°C, water depth 40 cm, and ambient temperature 23 ± 1°C. After each session, animals were dried at room temperature for 15 minutes. The last training session was performed 48 hours before tissue sampling, and the last injection was performed 72 hours before tissue sampling. SPSS-22 was used for statistical analysis using one-way ANOVA and Tukey's post hoc test.
Results: NF-κB levels in Group 4 (doxorubicin + swimming - DS) were significantly lower than those in Group 1 (resting control - C), Group 3 (doxorubicin resting - DR), and Group 2 (swimming control - SC) (p<0.01). Also, TNF-α levels in Group 4 (DS) were significantly lower than those in Groups 1 (C), 3 (DR), and 2 (SC) (p<0.01).
Conclusion: Swimming exercise combined with doxorubicin administration has a significant effect on reducing inflammatory factors (TNF-α and NF-κB). Therefore, exercise is recommended as an anti-inflammatory intervention.
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Main Subjects
- Jemal, A., et al., Global cancer statistics. CA Cancer J Clin, 2011. 61(2): p. 69–90.DOI: 10.3322/caac.20107
- Carvalho, C., et al., Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem, 2009. 16(25): p. 3267–85 DOI: 10.2174/092986709788803312.
- Ferreira, A.L., L.S. Matsubara, and B.B. Matsubara, Anthracycline-induced cardiotoxicity. Cardiovasc Hematol Agents Med Chem, 2008. 6(4): p. 278–81 DOI: 10.2174/187152508785909474.
- Emamghoreishi, M., H.-R. Bokaee, and M. Keshavarz, CYP2A6 genetic polymorphism and its relation to risk of smoking dependence in male Iranians. Physiology and Pharmacology, 2009. 12(4): p. 296–306.
- Rendu, F., et al., Smoking related diseases: the central role of monoamine oxidase. Int J Environ Res Public Health, 2011. 8(1): p. 136–47. DOI: 10.3390/ijerph8010136
- Chen, Q.M., et al., Corticosteroids inhibit cell death induced by doxorubicin in cardiomyocytes: induction of antiapoptosis, antioxidant, and detoxification genes. Mol Pharmacol, 2005. 67(6): p. 1861–73. DOI: 10.1124/mol.104.003814
- Frias, M.A., et al., Native and reconstituted HDL protect cardiomyocytes from doxorubicin-induced apoptosis. Cardiovasc Res, 2010. 85(1): p. 118–26DOI: 10.1093/cvr/cvp289.
- Farajzadeh, D., S. Karimi-Gharigh, and S. Dastmalchi, Tumor necrosis factor-alpha and its inhibition strategies: review article. Tehran University Medical Journal, 2017. 75(3): p. 159–171 URL: http://tumj.tums.ac.ir/article-1-8092-fa.html.
- Simon, H.B., Exercise and Health: Dose and Response, Considering Both Ends of the Curve. Am J Med, 2015. 128(11): p. 1171–7DOI: 10.1016/j.amjmed.2015.05.012.
- King, P.T., Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer. Clin Transl Med, 2015. 4(1): 68. DOI: 10.1186/s40169-015-0068-z
- Qin, L., et al., Swimming attenuates inflammation, oxidative stress, and apoptosis in a rat model of dextran sulfate sodium-induced chronic colitis. Oncotarget, 2017. 8(5): p. 7391–7404. DOI: 10.18632/oncotarget.14080
- Jackson, A.S. and M.L. Pollock, Generalized equations for predicting body density of men. Br J Nutr, 1978. 40(3): p. 497–504. DOI: 10.1079/bjn19780152
- Calvé, A., et al., Cardiac response to doxorubicin and dexrazoxane in intact and ovariectomized young female rats at rest and after swim training. Am J Physiol Heart Circ Physiol, 2012. 302(10): p. H2048–57. DOI: 10.1152/ajpheart.01069.2011
- Thomas, N.E. and D.R. Williams, Inflammatory factors, physical activity, and physical fitness in young people. Scand J Med Sci Sports, 2008. 18(5): p. 543–56. DOI: 10.1111/j.1600-0838.2008.00824.x
- Taddei, S., et al., Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation, 2000. 101(25): p. 2896–901. DOI: 10.1161/01.cir.101.25.2896
- Guerassimov, A., et al., The development of emphysema in cigarette smoke-exposed mice is strain dependent. Am J Respir Crit Care Med, 2004. 170(9): 974–80DOI: 10.1164/rccm.200309-1270OC.
- Zhang, J., et al., Oxidative stress response induced by chemotherapy in leukemia treatment. Mol Clin Oncol, 2018. 8(3): p. 391–399 DOI: 10.3892/mco.2018.1549.
- Yang, H.L., et al., Early Moderate Intensity Aerobic Exercise Intervention Prevents Doxorubicin-Caused Cardiac Dysfunction Through Inhibition of Cardiac Fibrosis and Inflammation. Cancers (Basel), 2020. 12(5). DOI: 10.3390/cancers12051102
- Kooshki, M., et al., How Swimming Modulates Inflammatory Pathways in Pain, Neurodegenerative, and Metabolic Disorders. Brain Sciences, 2025. 15(10): p. 1121. DOI: 10.3390/brainsci15101121
- Shi, S., et al., Role of oxidative stress and inflammation-related signaling pathways in doxorubicin-induced cardiomyopathy. Cell Commun Signal, 2023. 21(1): p. 61. DOI: 10.1186/s12964-023-01077-5
- barzegari, H., et al., The Effect of Endurance Training on Some Inflammatory Markers in Male Smokers. Sport Physiology & Management Investigations, 2018. 10(2): 21–30. https://www.sportrc.ir/article_67067.html
- Lin, J.Y., et al., Swimming exercise stimulates IGF1/ PI3K/Akt and AMPK/SIRT1/PGC1α survival signaling to suppress apoptosis and inflammation in aging hippocampus. Aging (Albany NY), 2020. 12(8): p. 6852–6864. DOI: 10.18632/aging.103046
- Lila, M., et al., The effect of endurance training and consumption of nettle extract on the gene expression of BCL-2 and TNF-α in mice with melanoma. Journal of Plasma and Biomarkers, 2022. 15(2): p. 23–33. https://www.sid.ir/paper/1067428/en
- Khalesi, M., S. Mirdar, and A. Samadi, Reduction of Tumor Necrosis Factor Alpha and Nuclear Factor- Kappa B Gene Expression in Lung Tissue of Rats After a Period of Swimming Training. Sport Physiology, 2018. 10(37): p. 153–166. DOI: 10.22089/spj.2018.1153
- Kadoglou, N.P., et al., The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus. Eur J Cardiovasc Prev Rehabil, 2007. 14(6): p. 837–43. DOI: 10.1097/HJR.0b013e3282efaf50.
- Nicklas, B.J., et al., Exercise training and plasma C-reactive protein and interleukin-6 in elderly people. J Am Geriatr Soc, 2008. 56(11): p. 2045–52. DOI: 10.1111/j.1532-5415.2008.01994.x
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