Effect of regular aerobic exercise on serum levels of cTnI, TNF-α and apoptosis in cardiac ischemia-reperfusion injury of the rats
Subject Areas : Veterinary Clinical Pathology
1 - Associate Professor, Department of Pathobiology, Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran.
Keywords: Rat, HEART, Apoptosis, cTnI, Aerobic exercise, ischemia/reperfusion, TNF-&alpha, ,
Abstract :
The process of restoring blood flow to ischemic heart muscle is antithetically capable of inducing cardiac damage. Cardiac troponin I (cTnI) and tumor necrosis factor alpha (TNF-α) are the important biochemical parameters of cardiac tissue damage. The aim of this study was to evaluate the effects of short term and regular growing long term aerobic exercise on serum levels of cTnI and TNF-α in rats with Ischemia/Reperfusion (I/R) injury. For this purpose, forty male Wistar rats were randomly divided into four equal groups including: control, I/R, I/R with two weeks of aerobic exercise, and I/R with eight weeks of regular growing aerobic exercise groups. Aerobic exercise was performed 5 times per week on treadmill at speed of 10-25m/min for 10-30 minutes with the slope of 5 degrees. For induction of I/R injury, the left descending coronary artery was clamped for 30 minutes, thereafter blood flow was restored for 2 hours. Finally, after collection of blood samples from the retro-orbital plexus for cTnI and TNF-α measurements, all animals were euthanized. Histologic sections were created for TUNEL staining from the hearts. Regular growing long term aerobic exercise significantly (p<0.05) decreased the cTnI and TNF-α serum levels, which were increased due to I/R injury. Microscopically, the numbers of apoptotic cells were significantly (p<0.01) increased in I/R group compared to the control group. Regular growing long term aerobic exercise significantly decreased the number of apoptotic cells (p<0.05). The results showed regular growing long term aerobic exercise protects the cardiac tissue of rats from I/R injury. Conflict of interest: None declared.
References:
Bayat, Gh., Hajizadeh, S., Javan, M., Safari, F., Goudarzvand, M., Shokri S., et al. (2012). Effect of exercise and chronic administration of nandrolone decanoate on expression of rat heart sarcolemmal ATP- sensitive potassium channels. Feyz, Journal of Kashan University of Medical Sciences, 16(2): 102-111. [In Persian]
Bbunin, L. and Jaffe, A.S. (2005). Troponin: The biomarker of choice for the detection of cardiac injury. Canadian Medical Association Journal, 173: 1191-1202.
Bersohn, M. and Scheuer, J. (1978). Effect of ischemia on the performance of hearts from physically trained rats. American Journal of Physiology, 234(2): H215-218.
Bezzerides, V. and Rosenzweig, A. (2011). Saying yes to exercise and NO to cardiac injury. Circulation Research, 108: 1414-1416.
Brown, D.A. and Moor, R.L. (2007). Perspectives in innate and acquired cardioprotection: cardioprotection acquired through exercise. Journal of Applied Physiology, 103(5): 1894-1899.
Brown, D.A., Chicco, A.J., Jew, K.N., Johnson, M.S., Lynch, J.M., Watson, P.A., et al. (2005a). Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat. The Journal of Physiology, 569(Pt3): 913-924.
Brown, D.A., Jew, K.N., Spaagana, G.C., Musch, T.I. and Moore, R.L. (2003). Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart. Journal of Applied Physiology, 95(6): 2510-2518.
Brown, D.A., Lynch, J.M., Armstrong, C.J., Caruso, N.M., Ehlers, L.B., Johnson, M.S., et al. (2005b). Susceptibility of the heart to ischaemia–reperfusion injury and exercise-induced cardioprotection are sexdependent. The Journal of Physiology, 564(Pt2): 619-630.
Cesselli, D., Jakoniuk, I., Barlucchi, L., Beltrami, A.P., Hintze, T.H., Nadal-Ginard, B., et al. (2001). Oxidative stress–mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy. Circulation Research, 89: 279-286.
Chicco, A.J., Johnson, M.S., Armstrong, C.J., Lynch, J.M., Gillenwater, C.P., Moore, R.L., et al. (2007). Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart. American Journal of Physiology-Heart Circulatory Physiology, 292(5): H2432-2437.
Dawson, E., George, K., Shave, R., Whyte, G. and Ball, D. (2003). Does the human heart fatigue subsequent to prolonged exercise? Sports Medicine, 33: 365-380.
Doustar, Y. (2017). Effect of regular aerobic exercise on cardiac ischemia-reperfusion injury in the rats. Journal of Comparative Pathobiology, In Press. [In Persian]
Ferdinandy, P., Schulz, R. and Baxter, G.F. (2007). Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacological Reviews, 59: 418-458.
Foadoddini, M., Amir-Abadi Zadeh, M. and Ghiravani, Z. (2014). Cardioprotective effects of ranitidine against ischemiareperfusion injury in mice. Journal of Birjand University of Medical Sciences, 20(4): 346-356. [In Persian]
Foadoddini, M., Esmailidehaj, M., Mehrani, H., Sadraei, S.H., Golmanesh, L., Wahhabaghai, H., et al. (2011). Pretreatment with hyperoxia reduces in vivo infarct size and cell death by apoptosis with an early and delayed phase of protection. European Journal of Cardio-Thoracic Surgery, 39(2): 233-240.
French, J.P., Quindry, J.C., Falk, D.J., Staib, J.L., Lee, Y., Wang, K.K., et al. (2006). Ischemia-reperfusion-induced calpain activation and SERCA2a degradation are attenuated by exercise training and calpain inhibition. American Journal of Physiology-Heart Circulatory Physiology, 290(1): H128-136.
Gatta, L., Armani, A., Iellamo, F., Consoli, C., Molinari, F., Caminiti, G., et al. (2012). Effects of a short-term exercise training on serum factors involved in ventricular remodeling in chronic heart failure patients. International Journal of Cardiology, 155(3): 409-413.
Gottlieb, R.A. (2003). Mitochondrial signaling in apoptosis: Mitochondrial daggers to the breaking heart. Basic Research in Cardiology, 98: 242-249.
Gu, X., Wang, Z., Ye, Z., Lei, J., Li, L., Su, D., et al. (2014). Resveratrol, an activator of SIRT1, upregulates AMPK and improves cardiac function in heart failure. Genetics and Molecular Research, 13: 323-335.
Gupta, P., Kanwal, A., Putcha, U.K., Bulani, Y., Sojitra, B., Khatua, T.N., et al. (2013). Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication. Journal of Translational Medicine, 11: 80.
Ignarro, L.J., Balestrieri, M.L. and Napoli, C. (2007). Nutrition, physical activity, and cardiovascular disease: an update. Cardiovascular Research, 73: 326-340.
Irwin, M.W., Mak, S., Mann, D.L., Qu, R., Penninger, J.M. and Yan, A. (1999). Tissue expression and immunolocalization of tumor necrosis factor-a in post infarction dysfunctional myocardium. Circulation, 99(11): 1492-1498.
Jesse, E., Adams, I. and Uickie, A. (1998). Cardiac Biomarkers: Past, present and future. American Journal of Critical Care, 7: 418-423.
Kevin, L.G., Novalija, E. and Stowe, D.F. (2005). Reactive oxygen species as mediators of cardiac injury and protection: the relevance to anesthesia practice. Anesthesia and Analgesia, 101(5): 1275-1287.
Lee, I.M., Sesso, H. and Paffenbarger, R.S. Jr. (2000). Physical activity and coronary heart disease risk in men: Does the duration of exercise episodes predict risk. Circulation, 102(9): 981-986.
Linke, A., Adams, V., Schulze, P.C., Erbs, S., Gielen, S., Fiehn, E., et al. (2005). Antioxidative effects of exercise training in patients with chronic heart failure increase in radical scavenger enzyme activity in skeletal muscle. Circulation, 111: 1763-1770.
Marefati, H., Aminizadeh, S., Najafipour, H., Dabiri, Sh. and Shahouzehi, B. (2016). The Effects of Moderate-Intensity Interval Training on the Resistance to Induced Cardiac Ischemia in Adult Male Rats. Qom University of Medical Science Journal, 10(4):1-9. [In Persian]
Moens, A.L., Chaeys, M.J., Timmermans, J.P. and Vrints, C.J. (2005): Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process. International Journal of Cardiology, 100: 179-190.
Mokni, M., Hamlaoui, S., Karkouch, I., Amri, M., Marzouki, L., Limam, F., et al. (2013). Resveratrol provides cardioprotection after ischemia/reperfusion injury via modulation of antioxidant enzyme activities. Iranian Journal of Pharmaceutical Research, 12(4): 867-875.
Neumayr, G., Pfister, R., Mitterbauer, G., Maurer, A., Gaenzer, H., Starm, W., et al. (2001). Effect of the race across the alps in elite cyclists on plasma cardiac troponins I and T. American Journal of Cardiology, 89: 484-486.
Ng, L.L., Loke, L.W., Davies, J.E., Geeranarar, S., Khunti, K., Stone, M.A., et al. (2005). Community screening for left reticular systolic dysfunction using plasma and urinary natriuretic peptides. Journal of the American College of Cardiology, 45: 1043-1050.
Owbeer, C.L., Seeberger, A., Gustafsson, S.A., Bouvier, F. and Hulting, J. (2007). Serum cardiac troponin T, troponin I, plasma BNP and left ventricular mass index in professional football players. Journal of Science and Medicine in Sport, 10(5): 291-296.
Powers, S.K., Demirel, H.A., Vincent, H.K., Coombes, J.S., Naito, H., Hamilton, K.L., et al. (1998). Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. American Journal of Physiology, 275(5 Pt 2): 1468-1477.
Powers, S.K., Quindry, J.C. and Kavazis, A.N. (2008). Exercise induced cardioprotection against myocardial ischemia-reperfusion injury. Free Radical Biology and Medicine, 44(2): 193-201.
Sack, M.N. (2002).Tumor necrosis factor-a in cardiovascular biology and the potential role for anti-tumor necrosis factor-a therapy in heart disease. Pharmacology and Therapeutics, 94(1-2): 123-135.
Sato, Y., Kita, T., Takatsu, Y. and Kimura, T. (2004). Biochemical markers of myocyte injury in heart failure. Heart, 90: 1110-1113.
Sawyer, D.B., Siwik, D.A., Xiao, L., Pimentel, D.R., Singh, K. and Colucci, W.S. (2002). Role of oxidative stress in myocardial hypertrophy and failure. Journal of Molecular and Cellular Cardiology, 34: 379-388.
Siu, P.M., Bryner, R.W., Martyn, J.K. and Alway, S.E. (2004). Apoptotic adaptations from exercise training in skeletal and cardiac muscles. Federation of American Societies for Experimental Biology Journal, 18: 1150-1152.
Soozani, Sh., Nazarali, P., Hanachi, P. and Shemshaki, A. (2010). Evaluation of cardiac troponin and creatine kinase in a long endurance training sessions in three female top athletes. Exercise Physiology, 1(2): 38-44. [In Persian]
Szabolcs, M., Michler, R.E., Yang, X., Aji, W., Roy, D., Athan, E., et al. (1996). Apoptosis of cardiac myocytes during cardiac allograft rejection: Relation to induction of nitric oxide synthase. Circulation, 94: 1665-1673.
Thompson, W.R. (2010). American College of Sports Medicine. In: ACSM's Guidelines for Exercise Testing and Prescription. 8th ed., Gordon, N.F. and Pescatello, L.S. editors. Philadelphia: Lippincott, Williams & Wilkings, pp: 580-640.
Tofighi A., Ebrahimi Kalan, A. and Jamali Qarakhanlou, B. (2015). The effect of resveratrol supplementation and aerobic training on cardiac tissue alteration of rats with acute myocardial infarction. Iranian Journal of Physiology and Pharmacology, 1(4): 135-145. [In Persian]
Van Dijk, A., Krijnen, P.A., Vermond, R.A., Pron, K.A., Spreeuwenberg, M., Visser, F.C., et al. (2009). Inhibition of type 2A secretory phospholipase A2 reduces death of cardiomyocytes in acute myocardial infarction. Apoptosis, 14: 753-763.
Zhou, B., Wu, L.J., Li, L.H., Tashiro, S., Onodera, S., Uchiumi, F., et al. (2006). Silibinin protects against isoproterenol-induced rat cardiac myocyte injury through mitochondrial pathway after up-regulation of SIRT1. Journal of Pharmacological Sciences, 102: 387-395.
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Bayat, Gh., Hajizadeh, S., Javan, M., Safari, F., Goudarzvand, M., Shokri S., et al. (2012). Effect of exercise and chronic administration of nandrolone decanoate on expression of rat heart sarcolemmal ATP- sensitive potassium channels. Feyz, Journal of Kashan University of Medical Sciences, 16(2): 102-111. [In Persian]
Bbunin, L. and Jaffe, A.S. (2005). Troponin: The biomarker of choice for the detection of cardiac injury. Canadian Medical Association Journal, 173: 1191-1202.
Bersohn, M. and Scheuer, J. (1978). Effect of ischemia on the performance of hearts from physically trained rats. American Journal of Physiology, 234(2): H215-218.
Bezzerides, V. and Rosenzweig, A. (2011). Saying yes to exercise and NO to cardiac injury. Circulation Research, 108: 1414-1416.
Brown, D.A. and Moor, R.L. (2007). Perspectives in innate and acquired cardioprotection: cardioprotection acquired through exercise. Journal of Applied Physiology, 103(5): 1894-1899.
Brown, D.A., Chicco, A.J., Jew, K.N., Johnson, M.S., Lynch, J.M., Watson, P.A., et al. (2005a). Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat. The Journal of Physiology, 569(Pt3): 913-924.
Brown, D.A., Jew, K.N., Spaagana, G.C., Musch, T.I. and Moore, R.L. (2003). Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart. Journal of Applied Physiology, 95(6): 2510-2518.
Brown, D.A., Lynch, J.M., Armstrong, C.J., Caruso, N.M., Ehlers, L.B., Johnson, M.S., et al. (2005b). Susceptibility of the heart to ischaemia–reperfusion injury and exercise-induced cardioprotection are sexdependent. The Journal of Physiology, 564(Pt2): 619-630.
Cesselli, D., Jakoniuk, I., Barlucchi, L., Beltrami, A.P., Hintze, T.H., Nadal-Ginard, B., et al. (2001). Oxidative stress–mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy. Circulation Research, 89: 279-286.
Chicco, A.J., Johnson, M.S., Armstrong, C.J., Lynch, J.M., Gillenwater, C.P., Moore, R.L., et al. (2007). Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart. American Journal of Physiology-Heart Circulatory Physiology, 292(5): H2432-2437.
Dawson, E., George, K., Shave, R., Whyte, G. and Ball, D. (2003). Does the human heart fatigue subsequent to prolonged exercise? Sports Medicine, 33: 365-380.
Doustar, Y. (2017). Effect of regular aerobic exercise on cardiac ischemia-reperfusion injury in the rats. Journal of Comparative Pathobiology, In Press. [In Persian]
Ferdinandy, P., Schulz, R. and Baxter, G.F. (2007). Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and postconditioning. Pharmacological Reviews, 59: 418-458.
Foadoddini, M., Amir-Abadi Zadeh, M. and Ghiravani, Z. (2014). Cardioprotective effects of ranitidine against ischemiareperfusion injury in mice. Journal of Birjand University of Medical Sciences, 20(4): 346-356. [In Persian]
Foadoddini, M., Esmailidehaj, M., Mehrani, H., Sadraei, S.H., Golmanesh, L., Wahhabaghai, H., et al. (2011). Pretreatment with hyperoxia reduces in vivo infarct size and cell death by apoptosis with an early and delayed phase of protection. European Journal of Cardio-Thoracic Surgery, 39(2): 233-240.
French, J.P., Quindry, J.C., Falk, D.J., Staib, J.L., Lee, Y., Wang, K.K., et al. (2006). Ischemia-reperfusion-induced calpain activation and SERCA2a degradation are attenuated by exercise training and calpain inhibition. American Journal of Physiology-Heart Circulatory Physiology, 290(1): H128-136.
Gatta, L., Armani, A., Iellamo, F., Consoli, C., Molinari, F., Caminiti, G., et al. (2012). Effects of a short-term exercise training on serum factors involved in ventricular remodeling in chronic heart failure patients. International Journal of Cardiology, 155(3): 409-413.
Gottlieb, R.A. (2003). Mitochondrial signaling in apoptosis: Mitochondrial daggers to the breaking heart. Basic Research in Cardiology, 98: 242-249.
Gu, X., Wang, Z., Ye, Z., Lei, J., Li, L., Su, D., et al. (2014). Resveratrol, an activator of SIRT1, upregulates AMPK and improves cardiac function in heart failure. Genetics and Molecular Research, 13: 323-335.
Gupta, P., Kanwal, A., Putcha, U.K., Bulani, Y., Sojitra, B., Khatua, T.N., et al. (2013). Cardioprotective effect of ritonavir, an antiviral drug, in isoproterenol induced myocardial necrosis: a new therapeutic implication. Journal of Translational Medicine, 11: 80.
Ignarro, L.J., Balestrieri, M.L. and Napoli, C. (2007). Nutrition, physical activity, and cardiovascular disease: an update. Cardiovascular Research, 73: 326-340.
Irwin, M.W., Mak, S., Mann, D.L., Qu, R., Penninger, J.M. and Yan, A. (1999). Tissue expression and immunolocalization of tumor necrosis factor-a in post infarction dysfunctional myocardium. Circulation, 99(11): 1492-1498.
Jesse, E., Adams, I. and Uickie, A. (1998). Cardiac Biomarkers: Past, present and future. American Journal of Critical Care, 7: 418-423.
Kevin, L.G., Novalija, E. and Stowe, D.F. (2005). Reactive oxygen species as mediators of cardiac injury and protection: the relevance to anesthesia practice. Anesthesia and Analgesia, 101(5): 1275-1287.
Lee, I.M., Sesso, H. and Paffenbarger, R.S. Jr. (2000). Physical activity and coronary heart disease risk in men: Does the duration of exercise episodes predict risk. Circulation, 102(9): 981-986.
Linke, A., Adams, V., Schulze, P.C., Erbs, S., Gielen, S., Fiehn, E., et al. (2005). Antioxidative effects of exercise training in patients with chronic heart failure increase in radical scavenger enzyme activity in skeletal muscle. Circulation, 111: 1763-1770.
Marefati, H., Aminizadeh, S., Najafipour, H., Dabiri, Sh. and Shahouzehi, B. (2016). The Effects of Moderate-Intensity Interval Training on the Resistance to Induced Cardiac Ischemia in Adult Male Rats. Qom University of Medical Science Journal, 10(4):1-9. [In Persian]
Moens, A.L., Chaeys, M.J., Timmermans, J.P. and Vrints, C.J. (2005): Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process. International Journal of Cardiology, 100: 179-190.
Mokni, M., Hamlaoui, S., Karkouch, I., Amri, M., Marzouki, L., Limam, F., et al. (2013). Resveratrol provides cardioprotection after ischemia/reperfusion injury via modulation of antioxidant enzyme activities. Iranian Journal of Pharmaceutical Research, 12(4): 867-875.
Neumayr, G., Pfister, R., Mitterbauer, G., Maurer, A., Gaenzer, H., Starm, W., et al. (2001). Effect of the race across the alps in elite cyclists on plasma cardiac troponins I and T. American Journal of Cardiology, 89: 484-486.
Ng, L.L., Loke, L.W., Davies, J.E., Geeranarar, S., Khunti, K., Stone, M.A., et al. (2005). Community screening for left reticular systolic dysfunction using plasma and urinary natriuretic peptides. Journal of the American College of Cardiology, 45: 1043-1050.
Owbeer, C.L., Seeberger, A., Gustafsson, S.A., Bouvier, F. and Hulting, J. (2007). Serum cardiac troponin T, troponin I, plasma BNP and left ventricular mass index in professional football players. Journal of Science and Medicine in Sport, 10(5): 291-296.
Powers, S.K., Demirel, H.A., Vincent, H.K., Coombes, J.S., Naito, H., Hamilton, K.L., et al. (1998). Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat. American Journal of Physiology, 275(5 Pt 2): 1468-1477.
Powers, S.K., Quindry, J.C. and Kavazis, A.N. (2008). Exercise induced cardioprotection against myocardial ischemia-reperfusion injury. Free Radical Biology and Medicine, 44(2): 193-201.
Sack, M.N. (2002).Tumor necrosis factor-a in cardiovascular biology and the potential role for anti-tumor necrosis factor-a therapy in heart disease. Pharmacology and Therapeutics, 94(1-2): 123-135.
Sato, Y., Kita, T., Takatsu, Y. and Kimura, T. (2004). Biochemical markers of myocyte injury in heart failure. Heart, 90: 1110-1113.
Sawyer, D.B., Siwik, D.A., Xiao, L., Pimentel, D.R., Singh, K. and Colucci, W.S. (2002). Role of oxidative stress in myocardial hypertrophy and failure. Journal of Molecular and Cellular Cardiology, 34: 379-388.
Siu, P.M., Bryner, R.W., Martyn, J.K. and Alway, S.E. (2004). Apoptotic adaptations from exercise training in skeletal and cardiac muscles. Federation of American Societies for Experimental Biology Journal, 18: 1150-1152.
Soozani, Sh., Nazarali, P., Hanachi, P. and Shemshaki, A. (2010). Evaluation of cardiac troponin and creatine kinase in a long endurance training sessions in three female top athletes. Exercise Physiology, 1(2): 38-44. [In Persian]
Szabolcs, M., Michler, R.E., Yang, X., Aji, W., Roy, D., Athan, E., et al. (1996). Apoptosis of cardiac myocytes during cardiac allograft rejection: Relation to induction of nitric oxide synthase. Circulation, 94: 1665-1673.
Thompson, W.R. (2010). American College of Sports Medicine. In: ACSM's Guidelines for Exercise Testing and Prescription. 8th ed., Gordon, N.F. and Pescatello, L.S. editors. Philadelphia: Lippincott, Williams & Wilkings, pp: 580-640.
Tofighi A., Ebrahimi Kalan, A. and Jamali Qarakhanlou, B. (2015). The effect of resveratrol supplementation and aerobic training on cardiac tissue alteration of rats with acute myocardial infarction. Iranian Journal of Physiology and Pharmacology, 1(4): 135-145. [In Persian]
Van Dijk, A., Krijnen, P.A., Vermond, R.A., Pron, K.A., Spreeuwenberg, M., Visser, F.C., et al. (2009). Inhibition of type 2A secretory phospholipase A2 reduces death of cardiomyocytes in acute myocardial infarction. Apoptosis, 14: 753-763.
Zhou, B., Wu, L.J., Li, L.H., Tashiro, S., Onodera, S., Uchiumi, F., et al. (2006). Silibinin protects against isoproterenol-induced rat cardiac myocyte injury through mitochondrial pathway after up-regulation of SIRT1. Journal of Pharmacological Sciences, 102: 387-395.
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