The Preventive Effect of Aerobic Exercise on Doxorubicin-Induced Tissue Toxicity: Histological Evidence of Old and Young Rat Lung Tissue

Document Type : Research Paper

Authors
Seyedeh Zoleikha Hashemi Chashmi 1
Valiolah dabidi Roshan 2
Soheil Azizi 3
1 Assistant Professor of Exercise Physiology, Payame Noor University, Tehran, Iran
2 Professor of Exercise Physiology, Faculty of Sports Sciences, Mazandaran University, Babolsar, Iran
3 Assistant Professor of Laboratory Sciences, School of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran
10.22089/spj.2020.8996.2039
Abstract
The toxic effects of Doxorubicin on various tissues from one hand, and the pre-treatment effects of exercise activity before the DOX induction on heart and liver tissues in young rats from other hand have already been recognized, but the pre-treatment effects of exercise on elderly rats, especially in the lung tissue is not well understood. The purpose of the present study was to compare changes in lung tissue following DOX intoxication and the preventive effect of aerobic exercise. 48 young (3 months) and elderly (32 months) male rats were divided into three subgroups: control (307.8, 374.8), DOX (422.368, 430) and DOX + exercise (372.370, 383). Training groups r an on treadmill for three weeks at a speed of 15-17 m/min and a time of 25-39 minutes and five sessions per week.  DOX receiver groups received DOX solution (20 mg / kg) 24 hours after the last exercise. 48 hours after DOX injection, biopsy and descriptive analysis were performed. Histological examination of lung tissue showed inflammation, intercellular edema, vascular congestion, increased vascular wall thickness in DOX induction groups and with more degradation in the elderly groups. Performing aerobic exercise pre-treatment in both groups improved the injuries caused by DOX. The findings showed that induction of DOX caused more damage to the lung tissue of elderly rats than young rats, because the resistance of elderly lung tissue to DOX was lower and pre-treatment with aerobic exercise mitigated the destructive effect of DOX on lung tissue and this healing is more evident in elderly lungs.
Keywords
Pulmonary Toxicity
Doxorubicin
Aerobic Exercise
Old and Young Rats

Main Subjects

  1. Siegel R L, Miller KD, Ahmedin J. Cancer statistics. CA Cancer J Clin; 2020.;70(1):7-30
  2. Sadat-Hoseini SK, DabidiRoshan V, ShojaeiShahrokhababdi M. Effects of time courses of treadmill training in tissue toxicity induced by Different doses of DOXorubicin in multiple organs. Razi Journal of Medical Sciences. 2017;23(151):31-42. (In Persian).
  3. Kalyanaraman B. Teaching the basics of the mechanism of Doxorubicin-induced cardiotoxicity: Have we been barking up the wrong tree? Re DOX Biology. 2020; 29:1-9.
  4. Peng Xia, Jingrui Chen, Yuening Liu, Maya Fletcher, Brian C. J, Zhaokang Cheng. DOXorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1. J Biol Chem. 2020; 29:1-21.
  5. Mancilla TR, Iskara B, Anne GJ. Doxorubicin-Induced Cardiomyopathy in Children. ComprPhysiol. 2020; 6: 1-54.
  6. Azizi S, Hashemichashmi Z, Dabidiroshan V, Zolfagharzade F, Parsai A. Heart Tissue changes following Doxorubicin toxicity: an experimental study on the protective effect of aerobic training in young and old rats. Scientific Journal of Ilam University of Medical Sciences. 2017; 30: 34-41.
  7. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013; 75: 685-705.
  8. Fu C, Wang T, Wang Y, Chen X, Jiao J, Ma F, et al. Metabonomics study of the protective effects of green tea polyphenols on aging rats induced by d-galactose. J Pharm Biomed Anal. 2011; 55(5):1067-74.
  9. Carvalho FS, Burgeiro A, Garcia R, Moreno AJ, Carvalho RA, Oliveira PJ. Doxorubicin-induced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy. Medicinal Research Reviews. 2014; 34(1):106–35.
  10. Smuder A J. Exercise stimulates beneficial adaptations to diminish Doxorubicin induced cellular toxicity. Applied Physiology and Kinesiology. 2019;1: 317(5): 662–72
  11. Ahmadian M, DabidiRoshan V, Leicht AS. Age-related effect of aerobic exercise training on antioxidant and oxidative markers in the liver challenged by Doxorubicin in rats. Free Radic Res. 2018; 52: 775-82.
  12. Dadban SM, Dabidi RV, Farazmandfa T. Effect of continuous aerobic exercise on Bax/ Bcl-2 ratio and Doxorubicin-induced liver toxicity in aging model rats. J MazandaranUniv Med Sci. 2018; 28(165):36-46. (In Persian).
  13. Ibrahim KM, Mantawy EM, Elanany MM. Abdelgawad HS, Khalifa Hussien NM. Alagroudy NN, El-demerdash E. Protection from Doxorubicin-induced nephrotoxicity by clindamycin: novel antioxidant, anti-inflammatory and anti-apoptotic roles. Naunyn-Schmiedeberg's Archives of Pharmacology. 2019; 1-10.
  14. Ayla S, Ismail S, Tanriverdi G, Cengiz M, Eser M, Soner B C, Oktem G. Doxorubicin induced nephrotoxicity: protective effect of nicotinamide. International Journal of Cell Biology. 2011; 2011: 1-10.
  15. Jacobson TK, Howe MD, Schmidt B, Hinman JR, Escabí MA, Markus EJ. Hippocampal theta, gamma, and theta-gamma coupling: effects of aging, environmental change, and cholinergic activation. J Neurophysiol. 2013; 109(7):1852-65.
  16. Jacobson TK, Schmidt B, Hinman JR, Escabí MA, Markus EJ. Age-related decrease in theta and gamma coherence across dorsal CA1 pyramidale and radiatum layers. Hippocampus. 2015; 10. DOI: 10.1002/hipo.22439
  17. Ahrafi J, Roshan VD, Mahjoub S. Cardioprotective effects of aerobic regular exercise against Doxorubicin-induced oxidative stress in Rat. African Journal of Pharmacy and Pharmacology. 2012;6:2380-8
  18. Ascensao A, Magalh~aes J, Soares J, et al. Endurance exercise training attenuates morphological signs of cardiac muscle damage induced by Doxorubicin in male mice. Basic Appl Myol. 2006;16(1):27–35
  19. Wang L, Zhang TP, Zhang Y, Bi H L, Guan X M, Wang H X, et al. Protection against Doxorubicin-induced myocardial dysfunction in mice by cardiac-specific expression of carboxyl terminus of hsp70-interacting protein. Sci Rep. 2016; 6(28399), 1-14.
  20. Nasiri E, Hosseinimehr S, Azadbakht M, Akbari J, Enayati-fard R, Azizi S, et al. Effect of Malva Sylvestris cream on burn injury and wounds in rats. Avicen J Phytom. 2015; 5:341-54.
  21. Machado NG, Baldeiras I, Pereira GC, Pereira SP, Oliveira PJ. Sub-chronic administration of Doxorubicin to wistar rats results in oxidative stress and unaltered apoptotic signaling in the lung. Chem Biol Interact. 2010; 188(3):478–86.
  22. Rezaeyan A, Haddadi GH, Hosseinzadeh M. Evaluating superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and the histological changes of the lung tissue after γ-Irradiation in rats. Journal of Fasa University of Medical Sciences. 2016;6: 235-45. (In Persian).
  23. Hashemi Chashmi SZ, Dabidiroshan V. The effect of pretreatment of aerobic training on some of the pulmonary stress indices against the toxicity of Doxorubicin. Journal of Isfahan Medical School. 2020; 37(559):1422-7. (In Persian).
  24. Giuranno L, Ient J, Ruysscher DD, Vooijs MA. Radiation-induced lung injury. Frontiers in Oncology. 2019; 9(877): 1-16.
  25. Marks LB, Yu X, Vujaskovic Z, Jr WS, Folz R, Anscher MS. Radiation-induced lung injury. Seminars in Radiation Oncology. 2003; 13(3):333-45.
  26. Tahamtan R, Shabestani Monfared A, Tahamtani Y, Tavassoli A, Akmali M, Mosleh-Shirazi MA, et al. Radioprotective effect of melatonin on radiation-induced lung injury and lipid peroxidation in rats. Cell J. 2015; 17(1):111-20.
  27. Crivellato E, Beltrami CA, Mallardi F, Ribatti D. The mast cell: an active participant or an innocent bystander? Histology and Histopathology. 2004;19(1):259-70.
  28. Blirando K, Milliat F, Martelly I, Sabourin JC, Benderitter M, François A. Mast cells are an essential component of human radiation proctitis and contribute to experimental colorectal damage in mice. The American J of Path. 2011;178(2):640-51.
  29.  Parsaeifar A, Mazaheri Z, Dabidi RV. 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. Journal of Sport Biosciences. 2016; 9(4):489-99. (In Persian).
Sport Physiology
Volume 12, Issue 48
January 2021
Pages 105-116

  • Receive Date 07 June 2020
  • Revise Date 18 October 2020
  • Accept Date 25 November 2020