DOI QR코드

DOI QR Code

Is Short-term Exercise a Therapeutic Tool for Improvement of Cardioprotection Against DOX-induced Cardiotoxicity? An Experimental Controlled Protocol in Rats

  • Ashrafi, Javad (Department of Sport Physiology, College of Physical Education and Sport Sciences, University of Mazandaran) ;
  • Roshan, Valiollah Dabidi (Department of Sport Physiology, College of Physical Education and Sport Sciences, University of Mazandaran)
  • Published : 2012.08.31

Abstract

Background and Objective: Cardiotoxicity and oxidative stress is a life-threatening side effect of doxorubicin (DOX). We investigate the effects of short-term exercise as therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity in the rat. Methods: Wistar males (weighing $257{\pm}28g$) were divided into six groups: (1) control+placebo (2) control+DOX $10mg.kg^{-1}$ (3) control+DOX $20mg.kg^{-1}$ (4) training+placebo (5) training+ DOX$10mg.kg^{-1}$ (6) training+DOX $20mg.kg^{-1}$. Cardiotoxicity was induced by DOX (10 and $20mg.kg^{-1}$). The rats in groups 4, 5 and 6 experienced treadmill running of 25 to $39min.day^{-1}$ and 15 to $17m.min^{-1}$, 5 days/wk for 3 wk. At the end of the endurance training program, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, DOX $10mg.kg^{-1}$ and DOX $20mg.kg^{-1}$, respectively. Result: DOX administration (10 and $20mg.kg^{-1}$) caused significant increase in MDA and Apelin, an insignificant increase in NO and a significant decrease in SOD, as compared to the C+P group. Three weeks of the pretreatment endurance exercise resulted in a significant increase of Apelin and SOD, an insignificant increase of NO and an insignificant decrease of MDA, as compared to the C+P group. Furthermore, after three weeks of endurance training and DOX treatment with $10mg.kg^{-1}$ and $20mg.kg^{-1}$, a significant increase in apelin and SOD, and a significant decrease in MDA were detected in comparison to C+DOX10 and/or C+DOX20 groups. There was a significant difference between DOX$10mg.kg^{-1}$ and DOX$20mg.kg^{-1}$ treatments in MDA levels only. Conclusion: Pretreatment exercise may improve myocardial tolerance to DOX-induced cardiotoxicity by inhibition of oxidative stress and up-regulation of antioxidants in heart tissue.

Keywords

Cardiac toxicity;doxorubicin;oxidative stress;aerobic training;rat model

References

  1. Abdel-Moneim MO, Marwa MN, Amany AA, Omimah AN, Mohamed TK (2009). Effect of methimazole treatment on doxorubicin-induced cardiotoxicity in mice. Food Chem Toxico, 47, 2425-30. https://doi.org/10.1016/j.fct.2009.06.040
  2. Ascensao A, Magalhaes J, Soares J et al (2005). Endurance training attenuates doxorubicin-induced cardiac oxidative damage in mice. Int J Cardiol, 100, 451-60. https://doi.org/10.1016/j.ijcard.2004.11.004
  3. Ascensao A, Magalhaes J, Soares J et al (2006). Endurance exercise training attenuates morphological signs of cardiac muscle damage induced by doxorubicin in male mice. Basic Applied Myol, 16, 27-35.
  4. Ascensao A, Oliveira PJ, Magalhaes J (2012). Exercise as a beneficial adjunct therapy during Doxorubicin treatment- Role of mitochondria in cardioprotection. Int J Cardiol, 156, 4-10. https://doi.org/10.1016/j.ijcard.2011.05.060
  5. Babaei R, Ejtemaeemehr S, Tavangar S et al (2008). Morphine is protective against doxorubicin-induced cardiotoxicity in rat. Toxicology, 243, 96-10. https://doi.org/10.1016/j.tox.2007.09.026
  6. Cecen E, Dost T, Culhacı N et al (2011). Protective Effects of Silymarin against Doxorubicin-induced Toxicity. Asian Pac J Cancer Prev, 12, 2697-704.
  7. Chicco AJ, Schneider CM, Hayward R (2006). Exercise training attenuates acute doxorubicin-induced cardiac dysfunction. J Cardiovasc Pharmacol, 47, 182-9 https://doi.org/10.1097/01.fjc.0000199682.43448.2d
  8. Chicco AJ, Schneider CM, Hayward R (2005). Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heart. Am J Physiol Regul Integr Comp Physiol, 289, R424-43. https://doi.org/10.1152/ajpregu.00636.2004
  9. Dabidi Roshan V, Assali M, Hajizadeh Moghaddam Ak, Hosseinzadeh M, Myers J (2011). Exercise training and antioxidants: effects on rat heart tissue exposed to lead acetate. Int J Toxicol, 30, 190-6. https://doi.org/10.1177/1091581810392809
  10. Dabidi Roshan V, Ranjbar Sh, Hosseinzadeh M, Myers J (2011). Left ventricular oxidant and antioxidant markers induced by lifestyle modification in rats exposed to lead acetate. European Journal of Sport Science, 1-6, first article.
  11. Daniel S, Limson JL, Dairam A, Watkins GM, Daya S (2004). Through mental binding, curcumin protects against leadand cadmium- induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J Organic Chem, 98, 266-75.
  12. De Beer EL, Bottone AE, Voest EE (2001). Doxorubicin and mechanical performance of cardiac trabeculae after acute and chronic treatment: a review. Eur J Pharmacol, 415, 1-11.
  13. El-Sayed MA, Shehta AS, Ghada MS, El-Damarawy SL (2011). Amelioration of doxorubicin-induced cardiotoxicity by deferiprone in rats. Can J Physiol Pharmacol, 89, 269-76. https://doi.org/10.1139/y11-020
  14. Hitesh S, Gaurav P, Praful P, et al (2011). Beneficial effects of carbon monoxide-releasing molecule-2 (CORM-2) on acute doxorubicin cardiotoxicity in mice: Role of oxidative stress and apoptosis. Toxicol Appl Pharmacol, 253, 70-80. https://doi.org/10.1016/j.taap.2011.03.013
  15. Hydock DS, Lien CY, Schneider CM, Hayward R (2008). Exercise preconditioning protects against doxorubicin induced cardiac dysfunction. Med Sci Sports Exercise, 40, 808-17. https://doi.org/10.1249/MSS.0b013e318163744a
  16. In Duk J, Jang-Soon L, Seong YY et al (2002). Doxorubicin Inhibits the Production of Nitric Oxide by Colorectal Cancer Cells. Arch Pharmacal Res, 25, 691-6. https://doi.org/10.1007/BF02976946
  17. Ioanna A, Fragiska S, Efstathios KI et al. (2007). Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical oleuropein through suppression of oxidative and nitrosative stress, J Mol Cell Cardiol, 42, 549-58. https://doi.org/10.1016/j.yjmcc.2006.11.016
  18. Kanu Ch, Jianqing Z, Norman H, Joel SK (2010). Doxorubicin Cardiomyopathy. Cardiology, 115, 155-62 https://doi.org/10.1159/000265166
  19. Kavazis AN, Smuder AJ, Min K, Tumer N, Powers SK (2010). Short-term exercise training protects against doxorubicininduced cardiac mitochondrial damage independent of HSP72. Am J Physiol Heart Circ Physiol, 5, 1515-24.
  20. Li L, Pan Q, Han W, et al (2007). Doxorubicin-induced oxidative stress in cardiomyocytes. Clin Cancer Res, 13, 6753-60. https://doi.org/10.1158/1078-0432.CCR-07-1579
  21. Mates JM (2000). Effect of antioxidant enzymes in the molecular control of reactive oxygen species. Toxicology, 153, 83-104. https://doi.org/10.1016/S0300-483X(00)00306-1
  22. Menna P, Salvatorelli E, Minotti G (2010). Anthracycline degradation in cardiomyocytes: a journey to oxidative survival. Chem Res Toxicol, 23, 6-10. https://doi.org/10.1021/tx9003424
  23. Raschi E, Vasina V, Ursino MG et al (2010). Anticancer drugs and cardiotoxicity: Insights and perspectives in the era of targeted therapy. Pharmacol Therapeutics, 125, 196-218. https://doi.org/10.1016/j.pharmthera.2009.10.002
  24. Teixeira de Lemos E, Pinto R, Oliveira J et al (2011). Differential effects of acute (extenuating) and chronic (training) exercise on inflammation and oxidative stress status in an animal model of type 2 diabetes mellitus. Mediators Inflamm, 25, 30-61.
  25. Verma N, Vinayak M (2012). A low dose of doxorubicin improves antioxidant defence system and modulates anaerobic metabolism during the development of lymphoma. IIndian J Pharmacol, 44, 308-13. https://doi.org/10.4103/0253-7613.96299
  26. Vishwanatha SA, Gulliaya S, Thippeswamy A, Basavaraj CK, Donnahalli VM (2012). Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. Indian J Pharmacol, 44, 73-7. https://doi.org/10.4103/0253-7613.91871
  27. Viswanatha Swamy AHM, Wangikar UBC, Koti AHM, Thippeswamy PMR, Manjula DV (2011). Cardioprotective effect of ascorbic acid on doxorubicin-induced myocardial toxicity in rats. Indian J Pharmacol, 43, 507-11. https://doi.org/10.4103/0253-7613.84952
  28. Wonders KY, Hydock DS, Greufe S, Schneider CM, Hayward R (2009). Endurance exercise training preserves cardiac function in rats receiving doxorubicin and the HER-2 inhibitor GW2974. Cancer Chem Pharmacol, 64, 1105-13. https://doi.org/10.1007/s00280-009-0967-z
  29. Xin YF, Wan LL, Peng JL, Guo Ch (2011). Alleviation of the acute doxorubicin-induced cardiotoxicity by Lyciumbarbarum polysaccharides through the suppression of oxidative stress. Food Chem Toxicol, 49, 259-64. https://doi.org/10.1016/j.fct.2010.10.028

Cited by

  1. Pretreatment Hepatoprotective Effect of Regular Aerobic Training Against Hepatic Toxicity Induced by Doxorubicin In Rats vol.14, pp.5, 2013, https://doi.org/10.7314/APJCP.2013.14.5.2931
  2. Exercise Prevention of Cardiovascular Disease in Breast Cancer Survivors vol.2015, pp.1687-8469, 2015, https://doi.org/10.1155/2015/917606
  3. Aerobic exercise in anthracycline-induced cardiotoxicity: a systematic review of current evidence and future directions vol.312, pp.2, 2017, https://doi.org/10.1152/ajpheart.00646.2016
  4. Aerobic Exercise During Early Murine Doxorubicin Exposure Mitigates Cardiac Toxicity vol.40, pp.3, 2018, https://doi.org/10.1097/MPH.0000000000001112
  5. TRPC channels in exercise-mimetic therapy pp.1432-2013, 2018, https://doi.org/10.1007/s00424-018-2211-3