اثر حفاظتی 6 هفته تمرین اختیاری بر آپوپتوز کبدی ناشی از دوکسوروبیسین در Ratهای مدل سالمندی

نوع مقاله : مقاله های پژوهشی

نویسندگان

1 دانشجوی دکتری فیزیولوژی ورزش، گروه تربیت بدنی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران

2 استاد، گروه فیزیولوژی ورزش، دانشکده‌ی علوم ورزشی، دانشگاه مازندران، بابلسر، ایران

3 استادیار، گروه پزشکی مولکولی، دانشکده‌ی فن‌آوری‌های نوین در علوم پزشکی و مرکز تحقیقات سلولی و مولکولی، دانشگاه علوم پزشکی گلستان، گرگان، ایران

چکیده

مقدمه: روش‌های تمرینی مختلفی جهت کاهش عوارض داروی دوکسوروبیسین ارایه شده‌اند که به نظر می‌رسد با توجه به شرایط بیماران، زمان شروع تمرینات، طول دوره و استرس تمرینی باید مورد توجه بیشتری قرار بگیرند. از این رو، هدف از انجام این مطالعه، بررسی اثر حفاظتی تمرین اختیاری بر آپوپتوز کبدی ناشی از دوکسوروبیسین در Ratهای مدل سالمندی بود.روش‌ها: 42 سر Rat بالغ نژاد Wistar، در 6 گروه (7 = n) شامل جوان، سالمند، سالمند + سالین، سالمند + دوکسوروبیسین، سالمند + دوکسوروبیسین + تمرین اختیاری و سالمند + سالین + تمرین اختیاری قرار گرفتند. تمرین اختیاری، در قفس‌های مجهز به چرخ دوار و شمارشگر مسافت، به مدت 6 هفته به صورت انفرادی و آزادانه انجام شد. هم‌زمان با 15 روز پایانی تمرین، دوکسوروبیسین یا محلول سالین با دز روزانه‌ی 1 میلی‌گرم/کیلوگرم (دز تجمعی 15 میلی‌گرم/کیلوگرم) تزریق شد. 48 ساعت پس از اتمام تمرین، بافت‌برداری از کبد برای ارزیابی بیان پروتئین‌های Bax و B-cell leukemia 2 (Bcl-2) جهت بررسی آپوپتوز به روش Western blot انجام شد.یافته‌ها: آزمون One-way ANOVA نشان داد در گروه‌های تمرینی نسبت به سایر گروه‌ها، میزان بیان پروتئین Bax و نسبت Bcl-2/Bax کاهش معنی‌دار و بیان پروتئین Bcl-2، افزایش معنی‌داری یافته بود.نتیجه‌گیری: تمرین اختیاری قبل و حین شیمی‌درمانی، ممکن است بتواند از طریق کاهش پروتئین Bax و نسبت Bcl-2/Bax، باعث کاهش آپوپتوز و افزایش بقا در هپاتوسیت‌های سالم سالمندان و در نتیجه، کاهش عوارض دوکسوروبیسین شود.

کلیدواژه‌ها

عنوان مقاله [English]

The Protective Effect of 6 Weeks of Voluntary Training on Liver Apoptosis Induced by Doxorubicin in Aging Model Rats

نویسندگان [English]

  • Minoo Dadban-Shahamat 1
  • Valiollah Dabidi-Roshan 2
  • Touraj Farazmandfar 3
1 PhD Student in Exercise Physiology, Department of Physical Education, Sari Branch, Islamic Azad University, Sari, Iran
2 Professor, Department of Exercise Physiology, School of Sport Sciences, University of Mazandaran, Babolsar, Iran
3 Assistant Professor, Department of Molecular Medicine, School of Advanced Medical Technologies AND Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran
چکیده [English]

Background: Different training methods have been presented to reduce the side effects of doxorubicin and it seems that according to patient's condition, the time to start exercises, and the duration and stress of exercise should be considered. This study aimed to investigate the preventive effect of voluntary exercise on liver apoptosis induced by doxorubicin in aging model rats.Methods: 42 adult male Wistar rats were divided into 6 equal groups of young, aging, aging + saline, aging + doxorubicin, aging + doxorubicin + voluntary training, and aging + saline+ voluntary training. Voluntary training was performed in cages equipped with a running wheel for six weeks individually and freely. At the same time, as the end of the training, doxorubicin or saline solution was injected with a cumulative dose (1 mg/kg). 48 hours after completion of the training, liver tissue sampling was performed to assess the apoptosis via examining the expression of Bax and B-cell leukemia 2 (Bcl-2) proteins using western blot method.Findings: One-way analysis of variance showed that in the training groups, the expression level of Bax protein and Bax/Bcl-2 ratio decreased significantly, and the expression of Bcl-2 protein was significantly increased in comparison to the control groups.Conclusion: Voluntary exercises prior to treatment with doxorubicin can reduce apoptosis and increase survival in healthy elderly hepatocytes via reducing the Bax protein and the Bax/Bcl-2 ratio, thereby reducing the side effects of doxorubicin.

کلیدواژه‌ها [English]

  • Exercise
  • Apoptosis
  • Doxorubicin
  • Aging, Bax protein
  • B-cell leukemia 2 family proteins

مراجع

  1. Smuder AJ, Kavazis AN, Min K, Powers SK. Doxorubicin-induced markers of myocardial autophagic signaling in sedentary and exercise trained animals. J Appl Physiol (1985) 2013; 115(2): 176-85.
  2. Pecorino L. Molecular biology of cancer: Mechanisms, targets, and therapeutics. Oxford, UK: Oxford University Press; 2008. p. 71-9.
  3. Afzalpour ME, Taheri Chadorneshin H. Physical activity and oxidative pressure. Tehran, Iran: Bamdad Ketab; 2014. p. 23-95. [In Persian].
  4. Dadban-Shahamat M. Cellular and molecular mechanisms of the effects of physical activity on cancer. Proceedings of the 5th National Conference on Applied Science in Sport; 2016 Dec 23; Ali Abad Katoul, Iran.
  5. Alexieva B, Sainova IV, Pavlova VG, Markova T, Nikolova EB. Insights into mechanisms of doxorubicin cardiotoxicity. J Phys Pharm Adv 2014; 4(3): 342-8.
  6. Salouege I, Ben AR, Ben SD, Elkadri N, Kourda N, Lakhal M, et al. Means of evaluation and protection from doxorubicin-induced cardiotoxicity and hepatotoxicity in rats. J Cancer Res Ther 2014; 10(2): 274-8.
  7. Zolfagharzadeh F, Roshan VD. Pretreatment hepatoprotective effect of regular aerobic training against hepatic toxicity induced by Doxorubicin in rats. Asian Pac J Cancer Prev 2013; 14(5): 2931-6.
  8. Alishahi A, Nasiri S. The protective effect of regular aerobic training on doxorubicin-induced hepatotoxicity in rats: the insulin-like growth factor system. Zahedan J Res Med Sci 2014; 16(12): 59-64.
  9. Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol 2004; 57(1): 6-14.
  10. Lu B, Chen H, Hong-Guang H. The relationship between apoptosis and aging. Adv Biosci Biotechnol 2012; 3(6):705-711.
  11. Ascensao A, Magalhaes J, Soares JM, Ferreira R, Neuparth MJ, Marques F, et al. Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. Am J Physiol Heart Circ Physiol 2005; 289(2): H722-H731.
  12. Ashrafi J, Dabidi Roshan V, Mahjoub S. Cardioprotective effects of aerobic regular exercise against doxorubicin-induced oxidative stress in rat. Afr J Pharm Pharmacol 2012; 6(31): 2380-8.
  13. Shirinbayan V, Dabidi-Roshan V, Mahjoub S. The therapeutic effect of endurance trainingon adriamycin-induced cardiac stress in rats. Journal of Health and Physical Activity 2013; 7(4): 8-17.
  14. Kim EJ, Hwang S. Effects of aerobic exercise on antioxidants in rat models with cardiomyopathy. Phys Ther Rehabil Sci 2015; 4(1):17-21.
  15. Huang CC, Chiang WD, Huang WC, Huang CY, Hsu MC, Lin WT. Hepatoprotective effects of swimming exercise against D-galactose-induced senescence rat model. Evid Based Complement Alternat Med 2013; 2013: 275431.
  16. Santana ET, Serra AJ, Silva Junior JA, Bocalini DS, Barauna VرG, Krieger JرE, et al. Aerobic exercise training induces an anti-apoptotic milieu in myocardial tissue. Motriz Revista de Educacao Fisica 2014; 20(2): 233-8.
  17. Kavazis AN, Smuder AJ, Min K, Tumer N, Powers SK. Short-term exercise training protects against doxorubicin-induced cardiac mitochondrial damage independent of HSP72. Am J Physiol Heart Circ Physiol 2010; 299(5): H1515-H1524.
  18. Chicco AJ, Schneider CM, Hayward R. Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heart. Am J Physiol Regul Integr Comp Physiol 2005; 289(2): R424-R431.
  19. Parsaeifar A, Dabidi Roshan V, Mazaheri Z. cardioprotective effect of voluntary physical activity on changes of doxorubicin-induced cardiac myosin heavy chain expression in aging model rats. J Urmia Univ Med Sci 2017; 27(10): 893-901. [In Persian].
  20. Kim SY, Lee J. Exercise training suppresses vascular fibrosis in aging obesity induced rats. J Exerc Nutrition Biochem 2014; 18(2): 175-80.
  21. Zhenjun T, Weixin X, Linong D. Effect of exercise training on expression of NOS, Bcl-2 and Bax in liver tissue of rats. Journal of Chengdu Sport University 2006; (5): 100-3.
  22. Chicco AJ, Hydock DS, Schneider CM, Hayward R. Low-intensity exercise training during doxorubicin treatment protects against cardiotoxicity. J Appl Physiol (1985) 2006; 100(2): 519-27.
  23. Sharifi F, Roshan V, Mazaheri Z. Effect of pretreatment of aerobic training on doxorubicin-induced left ventricular apoptosis gene expression in aging model rats. Modares J Med Sci Pathol 2016; 19(2): 29-43. [In Persian].
  24. Mohammadi Gorji S, Karimpour Malekshah AA. Effect of doxorubicin on Bcl2 and Bax expression in Rat heart. J Gorgan Univ Med Sci 2013; 15(1): 19-24. [In Persian].
  25. Yari R. Cell ageing and biotechnology. New Cellular and Molecular Biotechnology Journal 2011; 1(4): 7-26. [In Persian].
  26. Sadat-Hoseini SK, Dabidi Roshan V. Is sub-chronic exercise in Combination with medicinal nanoparticles a protective strategy against Doxorubicin-induced Hepatic oxidative stress and apoptosis in aging model rats? Nanomedicine Journal 2017; 4(4): 224-31.
  27. Halliwell B. Oxidative stress and neurodegeneration: Where are we now? J Neurochem 2006; 97(6): 1634-58.
  28. Javid AH, Dabidi Roshan V. Effects of six weeks of continuous training with and without nanocurcumin supplementation on doxorubicin-induced hepatotoxicity in an aging rat model. Pathobiology Research 2017; 19(4): 1-12. [In Persian].
  29. Kwak HB, Song W, Lawler JM. Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis, and remodeling in the rat heart. FASEB J 2006; 20(6): 791-3.
  30. Jafari A, Pourrazi H, Nikookheslat S, Baradaran B. Effect of exercise training on Bcl-2 and Bax gene expression in the rat heart. Gene, Cell and Tissue 2015; 2(4): e32833.
مجله دانشکده پزشکی اصفهان
دوره 36، شماره 465 - شماره پیاپی 465
فروردین و اردیبهشت 1397
صفحه 14-21

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سابقه مقاله

  • تاریخ دریافت: 06 دی 1396
  • تاریخ بازنگری: 11 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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