Pre-Treatment Effect of Voluntary Physical Activity on Cardiac Damage due to the Induction of Cumulative Doses of Doxorubicin in Aging Model Rats: Histopathological Examination of Heart Tissue

Parsaeifar, Ahmad; Mazaheri, Zohre; Dabidi Roshan, Valeyollah

doi:10.22059/jsb.2018.66074

Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license

Authors

¹ Ph.D of Exercise Physiology department, Faculty of Sport Sciences, Mazandaran University, Babolsar, Iran

² Assistant professor of anatomical sciences, Basic medical science research center, Histogenotechcompany, Tehran, Iran

³ . Professor of Exercise Physiology department, Faculty of Sport Sciences, Mazandaran University, Babolsar, Iran

https://doi.org/10.22059/jsb.2018.66074

Abstract

Reducing the effects of anthracyclines-induced cardiac toxicity is an effective strategy for more survival of cancer patients. This study aimed at investigating the pre-treatment effect of voluntary physical activity on cardiac damage due to the induction of cumulative doses of doxorubicin in aging model rats. 24 male Wistar rats (12 weeks old) were randomly divided into 3 groups: saline (S), doxorubicin (D), and voluntary physical activity (DWR). Ageing was induced by daily injection of D-galactose (100 mg/kg) for 9 weeks. 6 weeks of voluntary physical activity was performed on a wheel running. In the last 15 days of physical activity and D-galactose injection, doxorubicin with a cumulative dose of 15 mg/kg (or 1 mg/day) was injected. 48 hours after the end of physical activity and doxorubicin injection, the animals were euthanized and their left ventricles were severed for histological evaluation. The results showed that injection of doxorubicin insignificantly increased the apoptotic index and the ratio of heart weight to body weight while significantly decreased the ratio of fiber to the interstitial space (P<0.05). In addition, qualitative studies of the heart tissue revealed vacuolation, cell nucleus fragmentation, tissue structure cluttering, and cardiac fibers destruction. In contrast, voluntary physical activity before and during doxorubicin injection reduced these changes. Voluntary physical activity in combination with doxorubicin is an effective strategy to reduce doxorubicin-induced heart damage.

Keywords

References

1. Arola OJ, Saraste A, Pulkki K, Kallajoki M, Parvinen M, and Voipio-Pulkki L-M. Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer research. 2000; 60: 1789-1792.

2. Ascensão A, Magalhães J, Soares JM, Ferreira R, Neuparth MJ, Marques F, Oliveira PJ, and Duarte JA. Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. American Journal of Physiology-Heart and Circulatory Physiology. 2005; 289: H722-H731.

3. Ashrafi J, and Roshan VD. Is short-term exercise a therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity? An experimental controlled protocol in rats. Asian Pacific Journal of Cancer Prevention. 2012; 13: 4025-4030.

4. Ashrafi J, Roshan VD, and Mahjoub S. Cardioprotective effects of aerobic regular exercise against doxorubicin-induced oxidative stress in rat. African Journal of Pharmacy and Pharmacology. 2012; 6: 2380-2388.

5 Cove-Smith L, Woodhouse N, Hargreaves A, Kirk J, Smith S, Price SA, Galvin M, Betts CJ, Brocklehurst S, and Backen A. An integrated characterization of serological, pathological, and functional events in doxorubicin-induced cardiotoxicity. Toxicological Sciences. 2014; 140: 3-15.

6. Garber JC, Barbee RW, Bielitzki JT, Clayton L, Donovan J, Hendriksen C, Kohn D, Lipman N, Locke P, and Melcher J. Guide for the care and use of laboratory animals. The National Academic Press, Washington DC. 2011; 8: 220.

7. Hydock DS, Lien C-Y, Jensen BT, Parry TL, Schneider CM, and Hayward R. Rehabilitative exercise in a rat model of doxorubicin cardiotoxicity. Experimental biology and medicine. 2012; 237: 1483-1492.

8. Hydock DS, Wonders KY, Schneider CM, and Hayward R. Voluntary wheel running in rats receiving doxorubicin: effects on running activity and cardiac myosin heavy chain. Anticancer research. 2009; 29: 4401-4407.

9. Kavazis AN, Smuder AJ, Min K, Tümer N, and Powers SK. Short-term exercise training protects against doxorubicin-induced cardiac mitochondrial damage independent of HSP72. American Journal of Physiology-Heart and Circulatory Physiology. 2010; 299: H1515-H1524.

10. Kavazis AN, Smuder AJ, and Powers SK. Effects of short-term endurance exercise training on acute doxorubicin-induced FoxO transcription in cardiac and skeletal muscle. Journal of applied physiology. 2014; 117: 223-230.

11. Kelleni MT, Amin EF, and Abdelrahman AM. Effect of metformin and sitagliptin on doxorubicin-induced cardiotoxicity in rats: impact of oxidative stress, inflammation, and apoptosis. Journal of toxicology. 2015; 2015: 1-8.

12. Ki Y-K, Kim G-Y, and Kim E-J. Effects of cardiac biological activities on low-intensity physical training in doxorubicin-induced cardiotoxicity rat models. Physical Therapy Rehabilitation Science. 2014; 3: 107-111.

13. Kirkham AA. Exercise cardio-protection from chemotherapy for breast cancer. A dissertation submitted in partial fulfilment of the requirments for the degree of doctor of philosophy. University of British Columbia. 2016; 17- 19.

14. Lee J, Cho J-Y, and Kim W-K. Anti-inflammation effect of Exercise and Korean red ginseng in aging model rats with diet-induced atherosclerosis. Nutrition research and practice. 2014; 8: 284-291.

15. Mohamed AA, Khalil S, Nossier NS, and Khalil MS. Protective role of alpha-Lipoic acid against doxorubicin-induced cardiotoxicity in male albino rats [a light and transmission electron microscopy study]. Egyptian Journal of Histology [The]. 2009; 227-234.

16. Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, and Moens AL. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. Journal of molecular and cellular cardiology. 2012; 52: 1213-1225.

17. Parsaeifar A, Dabidi Roshan V, and Mazaheri Z. Cardiopreotective effect of voluntary physical activity on changes of doxorubicin-induced cardiac myosin heavy chain expression in aging model rats. urmia medical journal. 2017; 27: 893-901.

18. Shirinbayan V, Roshan VD, and Mahjoub S. The Therapeutic Effect of Endurance Training on Adriamycin-induced Cardiac Stress in Rats. Iranian Journal of Health and Physical Activity. 2013; 4: 8-17.

19. Smuder AJ, Kavazis AN, Min K, and Powers SK. Doxorubicin-induced markers of myocardial autophagic signaling in sedentary and exercise trained animals. Journal of applied physiology. 2013; 115: 176-185.

20. Swamy AV, Gulliaya S, Thippeswamy A, Koti BC, and Manjula DV. Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. Indian journal of pharmacology. 2012; 44: 73.

21. Swamy AV, Wangikar U, Koti B, Thippeswamy A, Ronad P, and Manjula D. Cardioprotective effect of ascorbic acid on doxorubicin-induced myocardial toxicity in rats. Indian journal of pharmacology. 2011; 43: 507.

22. van Waart H, Stuiver MM, van Harten WH, Geleijn E, Kieffer JM, Buffart LM, de Maaker-Berkhof M, Boven E, Schrama J, and Geenen MM. Effect of low-intensity physical activity and moderate-to high-intensity physical exercise during adjuvant chemotherapy on physical fitness, fatigue, and chemotherapy completion rates: results of the PACES randomized clinical trial. Journal of Clinical Oncology. 2015; 33: 1918-1927.

23. White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, and Henley SJ. Age and cancer risk: a potentially modifiable relationship. American journal of preventive medicine. 2014; 46: S7-S15.

Journal of Sport Biosciences

Pre-Treatment Effect of Voluntary Physical Activity on Cardiac Damage due to the Induction of Cumulative Doses of Doxorubicin in Aging Model Rats: Histopathological Examination of Heart Tissue

References

References

Volume 9, Issue 4
May 2016
Pages 489-499

Pre-Treatment Effect of Voluntary Physical Activity on Cardiac Damage due to the Induction of Cumulative Doses of Doxorubicin in Aging Model Rats: Histopathological Examination of Heart Tissue

References

References

Volume 9, Issue 4May 2016Pages 489-499

Volume 9, Issue 4
May 2016
Pages 489-499