تاثیر تمرین هوازی و مصرف نانو میسل کورکومین بر بیان ژن GPX ، Cat، SOD، MDA ،BAX و BCL2در بافت قلب موش های ماده بالب سی با سرطان پستان القایی در فاز درمانی با دوکسوروبیسین
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مجید مقیسه
ساناز میرزایان شانجانی
عبدالعلی بنائی فر
یاسر کاظم زاده
سعید صداقتی
ساناز میرزایان شانجانی
عبدالعلی بنائی فر
یاسر کاظم زاده
سعید صداقتی
چکیده
مقدمه: دوکسوروبیسین، دارویی فراگیر در درمان انواع سرطان‌ها است که به دلیل عوارض متعدد مصرف آن محدود شده است لذا پژوهش حاضر اثر تمرین هوازی و مصرف نانو‌میسل کورکومین بر میزان فعالیت BAX، BCL2 و غلظت MDA در مسمویت قلبی ناشی از دوکسوربیسین در موش‌های مبتلا به سرطان پستان بوده است.
شیوه‌ی مطالعه: در این پژوهش که از نوع بنیادی و از نظر کنترل متغیرها به صورت تجربی بود، 24 موش ماده بالب سی به‌طور تصادفي به 4 گروه بیمار دوکسوربیسین، بیمار دوكسوروبيسين و تمرين، بیمار دوكسوروبيسين و مکمل نانوکورکومین و بیمار دوكسوروبيسين، تمرين هوازي ومکمل تقسیم شدند. القاي سرطان پستان با سلول‌هاي MC4-L2 انجام شد. دوکسوروبيسين mg/kg2 به صورت زیرصفافی به تعداد 6 مرتبه و در روزهای 1، 7، 14، 21، 28 و 35 تزریق شد. برنامه‌ی هوازی 5 جلسه در هفته به مدت 42 روز با افزایش سرعت نوارگردان در هر دو هفته شامل 14، 16 و 18 متر بر دقیقه و مصرف نانوکورکومین با دوز mg/k100 بود. داده‌های جمع‌آوری شده با آنالیز واریانس دوطرفه و سطح معنیداری 0/05 انجام شد.
یافته‌ها: 6 هفته تمرین هوازی هیچ‌گونه تأثیری در فعالیت BCL2 و غلظت MDA نداشته بود ولی به‌طور معنیداری سبب کاهش میزان فعالیت BAX شده بود. مصرف مکمل نانوکورکومین به مدت 6 هفته سبب کاهش میزان فعالیت BAX و غلظت MDA و سبب افزایش معنی‌دار میزان فعالیت BCL2 شده بود. انجام 6 هفته تمرین هوازی به همراه مصرف مکمل نانوکورکومین بر میزان فعالیت BAX و غلظت MDA بی‌تأثیر بوده اما سبب افزایش فعالیت BCL2 شده بود (0/05 > p value).
نتیجه‌گیری: تمرین هوازی و مصرف مکمل نانوکورکورمین مجزا و یا همزمان می‌تواند در کاهش عوارض سمیت قلبی داروی دوکسوروبیسین در بیماران مبتلا به سرطان پستان مؤثر باشد.
کلمات کلیدی: تمرین هوازی دوکسوربیسین؛ سرطان پستان؛ نانو میسل کورکومین
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استناد به مقاله
مقیسهم., میرزایان شانجانیس., بنائی فرع., کاظم زادهی., & صداقتیس. (2023). تاثیر تمرین هوازی و مصرف نانو میسل کورکومین بر بیان ژن GPX ، Cat، SOD، MDA ،BAX و BCL2در بافت قلب موش های ماده بالب سی با سرطان پستان القایی در فاز درمانی با دوکسوروبیسین. مجله دانشکده پزشکی زابل, 71-82. Retrieved از http://jzms.ir/index.php/JZMS/article/view/395
نوع مقاله
مقاله پژوهشی
مراجع
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2. Ahmadian M, Dabidi Roshan V, Leicht AS. Age-related effect of aerobic exercise training on antioxidant and oxidative markers in the liver challenged by doxorubicin in rats. Free Radical Res 2018; 52(7): 775-82.
3. Xia P, Chen J, Liu Y, Fletcher M, Jensen B C, Cheng Z. Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1. J Biol Chem 2020; 295(13): 4265-76.
4. Alkuraishy HM, Al-Gareeb AI, Al-hussani HA. Doxorubicin-induced cardiotoxicity: Molecular mechanism and protection by conventional drugs and natural products. Inter J Clin Onco Can Res 2017; 2(2): 31-44.
5. Shirinbayan V, Dabidi Roshan V. Pretreatment effect of running exercise on HSP7 and DOX induced cardiotoxicity. Asian Pac J Cancer Prev 2012; 13(11): 5849-55.
6. van Deursen VM, Damman K, Hillege HL, van Beek AP, van Veldhuisen DJ, Voors AA. Abnormal liver function in relation to hemodynamic profile inheart failure patients. J Card Fail 2010; 16(1): 84-90.
7. Mohajeri M, Sahebkar A. Protective effects of curcumin against doxorubicin-induced toxicity and resistance: A review. Crit Rev Oncol Hematol 2018; 122: 30-51.
8. Hashemi Chashmi SZ, Dabidiroshan V. The effect of pretreatment of aerobic training on some of the pulmonary stress indices against the toxicity of doxorubicin [in Persian]. J Isfahan Med Sch 2020; 37(559): 1422-7.
9. Yap MY, Lo YL, Talbot K, Ong WY. Oxidative stress reduces levels of dysbindin-1A via its PEST domain. Neurochem Int 2014; 79: 65-9.
10. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics: American Cancer Society. CA Cancer J Clin 2005; 55(1): 10-30.
11. Ataollahi MR, Sharifi J, Paknahad MR, Paknahad A. Breast cancer and associated factors: A review. J Med Life 2015; 8(Spec Iss 4): 6-11.
12. Sadat-Hoseini SK, Dabidi Roshan V, Shojaei Shahrokhababdi M. Effects of time courses of treadmill training in tissue toxicity induced by Different doses of doxorubicin in multiple organs [in Persian]. Razi J Med Sci 2016; 23(151): 31-42.
13. Nagai K, Fukuno S, Oda A, Konishi H. Protective effects of taurine on doxorubicin-induced acute hepatotoxicity through suppression of oxidative stress and apoptotic responses. Anticancer Drugs 2016; 27(1): 17-23.
14. Lanari C, Lüthy I, Lamb CA, Fabris V, Pagano E, Helguero LA, et al. Five novel hormoneresponsive cell lines derived from murine mammary ductal carcinomas: in vivo and in vitro effects of estrogens and progestins. Cancer Res 2001; 61(1): 293-302.
15. Rogers LQ, Matevey C, Hopkins-Price P, Shah P, Dunnington G, Courneya KS. Exploring Social Cognitive Theory Constructs for Promoting Exercise Among Breast Cancer Patients. Cancer Nurs 2004; 27(6): 462-73.
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17. Saalu LC, Osinubi AA, Oguntola JA, Adeneye IO, Benebo AS. The delayed testicular morphologic effects of doxorubicin and the rejuvenating role of grapefruit seed extract. Int J Pharmacol 2010; 6(3): 192-99.
18. Takemura G, Fujiwara H. Doxorubicin-induced
cardiomyopathy from the cardiotoxic mechanisms to management. Prog Cardiovasc Dis 2007; 49(5): 330-52.
19. Dasgupta A, Nomura M, Shuck R, Yustein J. Cancer’s Achilles’ heel: apoptosis and necroptosis to the rescue. Int J Mol Sci 2016; 18(1): 23.
20. Bishayee A, Mandal A, Bhattacharyya P, Bhatia D. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis. Nutr Cancer 2016; 68(1): 120-30.
21. Ascensão A, Magalhães JM, Soares JMC, Ferreira R, Neuparth MJ, Marques F, et al. Moderateendurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. Am J Physiol Heart Circ Physiol 2005; 289: H722-31.
22. Marques-Aleixo I, Santos-Alves E, Torrella JR, Oliveira PJ, Magalhães J, Ascensão A. Exercise and doxorubicin treatment modulate cardiac mitochondrial quality control signaling. Cardiovasc Toxicol 2018; 18(1): 43-55.
23. Kavazis AN, Smuder AJ, Min K, Tümer N, Powers SK. Short-term exercise training protects againstdoxorubicin-induced cardiac mitochondrial damage independent of HSP72. Am J Physiol Heart Circ Physiol 2010; 299: H1515-24.
24. Héninger E, Krueger TEG, Lang JM. Augmenting antitumor immune responses with epigenetic modifying agents. Front Immunol 2015; 6: 29.
25. Injac R, Strukelj B, Recent advances in protection against doxorubicin-induced toxicity. Technol Cancer Res Treat 2008; 7(6): 497-516.El-Sayed EM, El-azeem ASA, Afify AA, Shabana MH, Ahmed HH. Cardioprotective effects of Curcuma longa L. extracts against doxorubicin-induced cardiotoxicity in rats. J Med Plants Res 2011; 5(17): 4049-58.
26. Katamura M, Iwai-Kanai E, Nakaoka M, Okawa Y, Ariyoshi M, Mita Y, et al. Curcumin attenuates doxorubicin-induced cardiotoxicity by inducing autophagy via the regulation of JNK Heidarzadeh phosphorylation. J Clin Exp Cardiolog 2014; 5: 9.
27. Heidarzadeh A, Ahadi AM, Panahi A, Sadeghizadeh M. Tumor suppressor p53 can protect normal cells against dendrosomal curcumin-induced apoptosis. Biomacromol J 2015; 1(2): 220-9.
28. Mohamad RH, El-Bastawesy AM, Zekry ZK, Al-Mehdar HA, Al-said MGAM, Aly SS, et al. The role of Curcuma longa against doxorubicin (adriamycin)-induced toxicity in rats. J Med Food 2009; 12(2): 394-402.
29. Brunet J, Barrett-Bernstein M, Zadravec K, Taljaard M, LeVasseur N, Srikanthan A, et al. Study protocol of the Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial: a two-arm, two-centre randomized controlled trial. BMC Cancer 2020; 20(1): 711.
30. Montalvo RN, Doerr V, Nguyen BL, Kelley RC, Smuder AJ. Consideration of sex as a biological variable in the development of doxorubicin myotoxicity and the efficacy of exercise as a therapeutic intervention. Antioxidants (Basel) 2021; 10(3): 343.
31. Prados J, Melguizo C, Ortiz R, Vélez C,
Alvarez PJ, Arias JL, et al. Doxorubicin-loaded nanoparticles: new advances in breast cancer therapy. Anticancer Agents Med Chem 2012; 12(9): 1058-70.
32. Wakefield ZR, Tanaka M, Pampo C, Lepler S, Rice L, Guingab-Cagmat J, et al. Normal tissue and tumor microenvironment adaptations to aerobic exercise enhance doxorubicin anti-tumor efficacy and ameliorate its cardiotoxicity in retired breeder mice. Oncotarget 2021; 12(18): 1737-48.