تأثیر تروگزروتین توأم با ورزش تناوبی شدید بر آسیب قلبی و بیان ژن‌های آنتی اکسیدانی در سمیت قلبی ناشی از دوکسوروبیسین در موشهای بزرگ آزمایشگاهی نر

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه تربیت بدنی و علوم ورزشی٬ واحد علوم و تحقیقات٬ دانشگاه آزاد اسلامی٬ تهران٬ ایران

2 گروه فیزیولوژی٬ دانشکده پزشکی و مرکز تحقیقات پزشکی مولکولی و تحقیقات کاربردی دارویی٬ دانشگاه علوم پزشکی تبریز٬ تبریز٬ ایران

چکیده

مقدمه و هدف: امروزه سرطان­ها به‌عنوان عامل مهم بیماری، باعث بیش از ۱۲ درصد از مرگ‌و‌میرها در جهان می­باشد. دوکسوروبیسین (­DOX)، داروی مؤثر در درمان انواع سرطان است که کاربرد آن به دلیل سمیت قلبی ناشی از دوز تجمعی به میزان زیادی محدود شده است. تروگزروتین (TRX) از فلاونوئیدروتین مشتق می­شود و خواص فارماکولوژیکی دارد. هدف از تحقیق حاضر بررسی تأثیر توأم تروگزروتین و تمرین HIIT در کاهش سمیت قلبی ناشی از DOX و بیان ژن­های آنتی­اکسیدانی در سلولهای قلبی رت­ها است.
مواد و روش ها: رت­های ویستار نر بصورت تصادفی در پنج گروه (۱۰n=) تقسیم شدند: ۱) Control، ۲) DOX، ۳) HIIT+DOX، ۴) ­TRX+DOX، ۵)­ ­HIIT+TRX+DOX. پس از آخرین تمرین HIIT، رتهای تمرین کرده و گروه کنترل مربوطه تحت تزریق داخل صفاقی DOX قرار­گرفتند. میزان تغییرات LDH و CKMB،با روش اسپکتوفوتومتری و تست الایزا و میزان بیان ژن­های آنتی­اکسیدانی با روش Real-Time PCR انداز­ه‎گیری شد.
نتایج: تزریق DOX میزان CKMB و LDH سرم را در رت­ها با سطح معنی­داری به ترتیب (۰۵/۰>P) و (۰۱/۰>P) افزایش داد. تمرین HIIT و مصرف تروگزروتین، هر کدام به تنهایی، میزان CKMBو LDH سرم را کاهش داد (۰۵/۰>P) و تأثیر توأم آنها بیشتر از هر­کدام به­تنهایی بود (۰۱/۰>P). تزریق DOX میزان بیان ژن­های­ آنتی­اکسیدانی Nrf2 و Foxo1 را کاهش داد (۰۱/۰>P). تمرین HIIT و مصرف تروگزروتین، هر کدام به تنهایی، میزان بیان ژن Foxo1 را افزایش داد (۰۵/۰>P) و تأثیر توأم آنها بیشتر از هر­کدام به­تنهایی بود (۰۱/۰>P). تمرین HIIT و مصرف تروگزروتین، هر کدام به تنهایی، میزان بیان ژن Nrf2 را بطور غیرمعنی­دار افزایش داد ولی تأثیر توأم آنها، افزایش معنی­دار بود (۰۱/۰>P).
نتیجه‌گیری: تأثیر توأم تمرین HIIT و تروگزروتین برای پیشگیری از سمیت قلبی ناشی از DOX و افزایش بیان ژن­های آنتی­اکسیدانی در سلول­های قلبی رت­ها مؤثرتر از کاربرد هریک از این راه‌کار­ها به­تنهایی می­باشد.

کلیدواژه‌ها


عنوان مقاله [English]

The effect of Troxerutin combined with high intensity interval training on heart injury and expression of antioxidant genes in doxorubicin-induced cardiac toxicity in male rats

نویسندگان [English]

  • Aboalghasem Taghavi Holagh 1
  • Hosein Aabednatanzi 1
  • Reza Badalzadeh 2
  • Farshad Ghazalian 1
1 Department of Physical Education and Sports Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
2 Department of Physiology, School of Medicine and Molecular Medical Research Center and Applied Pharmaceutical Research, Tabriz University of Medical Sciences, Tabriz, Iran.
چکیده [English]

Background and Objective: Cancers represent an important cause of morbidity and mortality, cause more than 12% of deaths in the world. Doxorubicin (DOX) is an effective drug in the treatment of various cancers whose usage has been limited due to cardiac toxicity. Troxerutin (TRX) is derived from rutin flavonoids and has multiplex pharmacological properties. The present study aimed to investigate the combined effect of troxerutin and high-intensity interval training (HIIT) on DOX-induced cardiac toxicity and the expression of antioxidant genes in rat hearts.
Materials and Methods: Male Wistar rats were randomly divided into five groups (n = 10): 1) Control, 2) DOX, 3) HIIT + DOX, 4) TRX + DOX, and 5) HIIT + TRX + DOX. After the last session of HIIT, the trained and time-matched control rats were injected with DOX (20 mg/kg, ip). The Creatine kinase (CKMB) and Lactate­dehydrogenase (LDH) changes were measured by spectrophotometry and ELISA. Expression of antioxidant genes was measured by Real-Time PCR.
Results: DOX injection increased serum CKMB and LDH in rats in comparison to the control group (p < 0.05) and (P <0.01), respectively. HIIT exercise and troxerutin, alone or in combination, reduced the serum CKMB and LDH levels (p < 0.05) and their combined effect was greater than those of individual treatments (p < 0.01). DOX injection decreased the expression of Nrf2 and Foxo1 antioxidant genes as compared with a control group (P <0.01). HIIT exercise and troxerutin consumption alone increased the expression of the Foxo1 gene as compared with the DOX group (P <0.05) and their combined effect was greater than either alone (P <0.01). HIIT exercise and troxergotTroxerutin consumption alone increased the expression of the Nrf2 gene insignificantly, but their combined effect was significantly increased (P <0.01).
Conclusion: The combined effect of HIIT exercise and troxerutin is a promising strategy to prevent DOX-induced cardiac toxicity and increase the expression of antioxidant genes in rat hearts.

کلیدواژه‌ها [English]

  • Doxorubicin
  • High-Intensity interval training
  • Troxerutin
  • Cardiac toxicity
  • Antioxidant Genes
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