نوع مقاله : مقاله پژوهشی
نویسندگان
1 دانشیار گروه علوم ورزشی، دانشکده علوم انسانی، دانشگاه ایلام، ایلام، ایران.
2 استادیار گروه تربیت بدنی و علوم ورزشی، دانشگاه پیام نور، تهران، ایران.
3 کارشناسی ارشد، گروه علوم ورزشی، دانشکده علوم انسانی، دانشگاه ایلام، ایلام، ایران.
چکیده
زمینه و هدف: استفاده همزمان از داروهای استاتینی و تمرینات استقامتی ممکن است اثربخشی بهتری در درمان و پیشگیری از ناهنجاریهای قلبی-عروقی از قبیل انفارکتوس میوکارد داشته باشد. هدف از پژوهش حاضر، بررسی اثر ترکیب تمرینات ورزشی استقامتی و مصرف داروی آتورواستاتین بر ویژگیهای اسپرم و سطح هورمونهای جنسی سرم موشهای صحرایی نر نژاد ویستار مبتلا به آنفارکتوس میوکارد بود. روش تحقیق: تعداد 28 سر موش صحرایی نر نژاد ویستار با وزن 250-210 گرم، بهطور تصادفی به چهار گروه مساوی (هفت سر موش در هر گروه) کنترل، آتورواستاتین، تمرین استقامتی، و آتورواستاتین+ تمرین استقامتی تقسیم شدند. برای ایجاد انفارکتوس میوکارد، از تزریق زیرجلدی ایزوپرنالین به میزان 150 میلیگرم/کیلوگرم وزن بدن در دو روز متوالی، استفاده شد. پس از القاء انفارکتوس میوکارد، برنامه تمرینی و مداخله دارویی آغاز گردید. برنامه تمرین ورزشی شامل دویدن روی نوارگردان (با سرعت 16-10 متر بر دقیقه و 50-10 دقیقه در روز) به مدت هشت هفته، پنج روز در هفته بود. گروههای آتورواستاتین و آتورواستاتین+ تمرین ورزشی؛ روزانه میزان 10 میلیگرم/کیلوگرم آتورواستاتین به صورت گاواژ دریافت کردند. 48 ساعت پس از آخرین جلسه تمرین، خونگیری و تشریح انجام شد. اندازهگیری شاخصهای سرمی با روش الایزا صورت گرفت. همچنین برای ارزیابی ویژگیهای اسپرمها، اپیدیدیم از بافت بیضه جدا و مورد بررسی قرار گرفت. نتایج با استفاده از آزمون تحلیل واریانس یک راهه و شفه در سطح معنیداری 05/0≥p استخراج گردید. یافتهها: تمرین استقامتی، مصرف آتورواستاتین و ترکیب تمرین و دارو، باعث کاهش معنیدار در تعداد اسپرم، درصد اسپرمهای زنده، میزان تحرک اسپرمها، سطح تستوسترون، هورمون لوتئینی (LH)، هورمون محرک فولیکول (FSH)، لیپوپروتئین با چگالی پایین (LDL)، کلسترول و تریگلیسرید سرمی؛ و افزایش معنیدار لیپوپروتئین با چگالی بالا (HDL) در رتهای مبتلا به آنفارکتوس میوکارد شد. نتیجهگیری: تمرین استقامتی، مصرف آتورواستاتین و ترکیب آنها، اگر چه موجب بهبود نیمرخ لیپیدی گردید، اما بر سطوح هورمونهای جنسی، نشانگرهای اسپرمی و در نتیجه عملکرد تولیدمثلی موشهای صحرایی نر مبتلا به آنفارکتوس میوکارد؛ اثر نامطلوب داشت.
کلیدواژهها
عنوان مقاله [English]
The effect of a course of endurance training with atorvastatin on some sex hormones and reproductive markers of male Wistar rats
نویسندگان [English]
- Nabi Shamsaei 1
- Hadi Abdi 2
- Zahra Abadi 3
1 Associate Professor at Department of Sports Sciences, Faculty of Humanities, Ilam University, Ilam, Iran.
2 Assistant Professor at Department of Sport Sciences, Payam-e Noor University, Tehran, Iran.
3 MSc of Exercise Physiology, Department of Sport Sciences, Faculty of Humanities, Ilam University, Ilam, Iran.
چکیده [English]
Extended Abstract
Background and Aim: Statins have specific effects on various body tissues in pathological conditions (3, 4). One of the most widely used statins is atorvastatin, which is used to treat and prevent cardiovascular abnormalities and also to treat high blood lipids (1, 7). A significant side effects of atorvastatin is the reduction of testosterone production.
Researchers has demonstrated that endurance training has an acute effect on hormonal response and chronic changes in basal hormone concentrations (16). Results indicate that endurance training reduces plasma cholesterol concentrations (17). Additionally, it has been shown that endurance training is associated with a decrease in testosterone levels (14).
Considering atorvastatin’s role in inhibiting cholesterol synthesis and the impact of endurance training in reducing plasma cholesterol concentration, along with the necessity of cholesterol for the synthesis of sex hormones, it appears that the simultaneous use of endurance training and statin drugs can cause disorders in the production of sex hormones through cholesterol reduction and ultimately reduce reproductive function. Therefore, the present study investigates the combined effects of endurance training and atorvastatin on sperm characteristics and sex hormone levels of male rats with myocardial infarction.
Materials and Methods: Twenty-eight male Wistar rats, weighing 210-250 g were prepared and divided into four groups: control, atorvastatin, endurance training, and atorvastatin combined with endurance training. All rats were maintained in standard environmental conditions with free access to water and food.
To induce myocardial infarction, rats were injected subcutaneously with 150 mg/kg of isoprenaline hydrochloride (Sigma, USA) daily for two days at 24-hour intervals (25). The control group received normal saline instead of isoprenaline for two days. Forty-eight after the induction of myocardial infarction, the exercise program and drug intervention began. The exercise program included treadmill running at a speed of 10-16 m/min for 10-50 minutes per day, five days a week, over a duration of eight weeks (26). The drug intervention groups received 10 mg/kg of atorvastatin dissolved in normal saline daily orally and by gavage. The other groups also received normal saline in the same amount.
Forty-eight hours after the last training session, the rats were anesthetized and blood was collected from their hearts. The blood samples were then centrifuged and their serum was separated and stored at -30°C for measurement of biochemical factors. The ELISA method was used to measure the levels of serum factors. To evaluate sperm characteristics, including sperm count, viability, and motility, the animals were dissected and their epididymis were separated from the testicular tissue and was examined.
All data were analyzed using SPSS software (version 22). A one-way analysis of variance (ANOVA) was performed, followed by the Scheffé post hoc test to compare differences between groups. A level of p≤0.05 was considered statistically significant.
Findings: The results of the sperm count indicated that sperm count in the experimental groups (atorvastatin (32.15±3.11), endurance training (34.01±2.72) and combination group (33.57±2.01) decreased significantly compared to the control group (49.41±2.28). However, there was no significant difference in sperm count among the experimental groups.
The analysis of live sperm count revealed that the percentage of live sperm in the experimental groups (atorvastatin: 63.47±3.01, endurance training: 65.41±2.83, and combination group: 64.12±2.12) also decreased significantly compared to the control group (83.25±2.74). Again, the differences in the percentage of live sperm among the experimental groups were not significant.
The results of the sperm motility showed that the rapid sperm motility rate in the experimental groups (atorvastatin, endurance training, combination) decreased compared to the control group, but the decrease was significant only in the atorvastatin and endurance training groups compared to the control group. The rapid sperm motility rate in the combination group was significantly different compared to the atorvastatin and exercise groups. Additionally, the percentage of non-motile sperm in the atorvastatin and exercise groups increased significantly compared to the control group. There was no significant difference between the combination group and the control group in terms of the percentage of non-motile sperm.
The results also indicated that the serum levels of testosterone, Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) in the endurance training group, the atorvastatin group and the combination group decreased significantly compared to the control group. Furthermore, the serum levels of HDL in the endurance training group, atorvastatin group, and the combination of endurance training and atorvastatin increased significantly compared to the control group. In contrast, the serum levels of LDL and cholesterol decreased significantly compared to the control group. The serum levels of triglycerides in the endurance training group decreased significantly compared to the control group.
Conclusion: The results of the present study demonstrated that while endurance training, atorvastatin and their combination improved lipid profile and reduced total cholesterol, they simultaneously caused disturbances in sperm parameters (sperm count, live sperm count and sperm motility) and decreased levels of sex hormones (testosterone, LH and FSH) in male rats with myocardial infarction.
It seems that the decrease in testosterone levels in the exercise and drug intervention groups in the present study is probably due to the effects of endurance training and atorvastatin on reducing cholesterol (a precursor of steroid hormones), which will disrupt the spermatogenesis process and, as a result, further reduce the number of spermatogonial cells. Such changes can lead to a decrease in reproductive activity in males.
Therefore, in situations where there is concern about infertility and reduced reproductive function, it is advisable to avoid the simultaneous and long-term use of statin drugs and endurance training. Alternative approaches should be considered to improve the lipid profile and reduce the risk of cardiovascular diseases.
Keywords: Exercise training, Atorvastatin, Infertility, Myocardial infarction.
Ethical considerations: This study has received ethical approval with the ID number IR.ILAM.REC.1402.002 from the Research Ethics Committee of Ilam University.
Compliance with ethical guideline: In this study, all experiments were conducted in accordance with the regulations of the Research Ethics Committee of Ilam University for animal studies.
Funding: This research project was funded by the Iran’s National Elites Foundation (Contract No. 841/4890).
Conflict of interest: None of the authors of this article have any conflicts of interest for its publication.
کلیدواژهها [English]
- Exercise training
- Atorvastatin
- Infertility
- Myocardial infarction.
2. Mooradian AD, Haas MJ, Batejko O, Hovsepyan M, Feman SS. Statins ameliorate endothelial barrier permeability changes in the cerebral tissue of streptozotocin-induced diabetic rats. Diabetes. 2005;54(10):2977-82. https://doi.org/10.2337/diabetes.54.10.2977
3. Grip O, Janciauskiene S, Bredberg A. Use of atorvastatin as an anti‐inflammatory treatment in Crohn’s disease. British Journal of Pharmacology. 2008;155(7):1085-92. https://doi.org/10.1038/bjp.2008.369
4. Li J, Sun YM, Wang LF, Li ZQ, Pan W, Cao HY. Comparison of effects of simvastatin versus atorvastatin on oxidative stress in patients with coronary heart disease. Clinical Cardiology: An International Indexed and Peer‐Reviewed Journal for Advances in the Treatment of Cardiovascular Disease. 2010;33(4):222-7. https://doi.org/10.1002/clc.20724
5. Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45(1):89-118. https://doi.org/10.1146/annurev.pharmtox.45.120403.095748
6. Goyal A, Singh S, Tandon N, Gupta N, Gupta YK. Effect of atorvastatin on pancreatic Beta-cell function and insulin resistance in type 2 diabetes mellitus patients: a randomized pilot study. Canadian Journal of Diabetes. 2014;38(6):466-72. https://doi.org/10.1016/j.jcjd.2014.01.006
7. Briand F, Magot T, Krempf M, Nguyen P, Ouguerram K. Effects of atorvastatin on high‐density lipoprotein apolipoprotein A‐I metabolism in dogs. European Journal of Clinical Investigation. 2006;36(4):224-30. https://doi.org/10.1111/j.1365-2362.2006.01669.x
8. Zhao S-p, Wu Z-h, Hong S-c, Ye H-j, Wu J. Effect of atorvastatin on SR-BI expression and HDL-induced cholesterol efflux in adipocytes of hypercholesterolemic rabbits. Clinica Chimica Acta. 2006;365(1-2):119-24. https://doi.org/10.1016/j.cca.2005.08.006
9. Kanat M, Serin E, Tunçkale A, Yildiz O, Sahin S, Bolayırlı M, et al. A multi-center, open label, crossover designed prospective study evaluating the effects of lipid lowering treatment on steroid synthesis in patients with Type 2 diabetes (MODEST Study). Journal of Endocrinological Investigation. 2009;32:852-6. https://doi.org/10.1007/bf03345757
10. Ramezani Moghadam M, Heydarieh N, Khoshsokhan M. The Effect of Atorvastatin on Depression by Forced Swimming Stress model in Gonadectomized Male Mice. SSU_Journals. 2016;24(5):429-40. [In Persian].
11. Dizaye KF, Ahmed SR. Combination of atorvastatin and fenofibrate altered androgenic activities of male rats. Zanco Journal of Medical Sciences (Zanco J Med Sci). 2019;23(2):264-73. https://doi.org/10.15218/zjms.2019.034
12. Akdeniz E, Onger ME, Bolat MS, Firat F, Gur M, Cinar O, et al. Effect of atorvastatin on spermatogenesis in rats: A stereological study. Tropical Journal of Pharmaceutical Research. 2020;19(12):2609-14. https://doi.org/10.4314/tjpr.v19i12.19
13. Klinefelter G, Laskey J, Amann R. Statin drugs markedly inhibit testosterone production by rat Leydig cells in vitro: Implications for men. Reproductive Toxicology. 2014;45:52-8. https://doi.org/10.1016/j.reprotox.2013.12.010
14. Wilund K, Feeney L, Tomayko E, Weiss E, Hagberg J. Effects of endurance exercise training on markers of cholesterol absorption and synthesis. Physiological Research. 2009;58(4). https://doi.org/10.33549/physiolres.931515
15. Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Medicine. 2005;35:339-61. https://doi.org/10.2165/00007256-200535040-00004
16. Chwalbinska-Moneta J, Kruk B, Nazar K, Krzeminski K, CI HK-U, KO AZ. Early effects of short-term endurance training. Journal of Physiology and Pharmacology. 2005;56(1):87-99.
17. Swain DP, Franklin BA. Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise. The American Journal of Cardiology. 2006;97(1):141-7. https://doi.org/10.1016/j.amjcard.2005.07.130
18. Mirghani J, Arshadi S, Ayaz A, Korpi JG, Fakourian A. Effect eight weeks strength, endurance and concurrent training on blood serum cortisol/testosterone ratio and muscular fitness in soldiers wrestler. Annals of Military and Health Sciences Research. 2013;11(3). [In Persian].
19. Maleki BH, Tartibian B, Chehrazi M. The effects of three different exercise modalities on markers of male reproduction in healthy subjects: a randomized controlled trial. Reproduction. 2017;153(2):157-74. https://doi.org/10.1530/rep-16-0318
20. Matos B, Howl J, Ferreira R, Fardilha M. Exploring the effect of exercise training on testicular function. European Journal of Applied Physiology. 2019;119:1-8. https://doi.org/10.1007/s00421-018-3989-6
21. Samadian Z, Tofighi A, Razi M, Tolouei Azar J, Ghaderi Pakdel F. Moderate‐intensity exercise training ameliorates the diabetes‐suppressed spermatogenesis and improves sperm parameters: Insole and simultaneous with insulin. Andrologia. 2019;51(11):e13457. https://doi.org/10.1111/and.13457
22. Toyama K, Sugiyama S, Oka H, Iwasaki Y, Sumida H, Tanaka T, et al. Combination treatment of rosuvastatin or atorvastatin, with regular exercise improves arterial wall stiffness in patients with coronary artery disease. PLoS One. 2012;7(7):e41369. https://doi.org/10.1371/journal.pone.0041369
23. Guazzi M, Tumminello G, Reina G, Vicenzi M, Guazzi M. Atorvastatin therapy improves exercise oxygen uptake kinetics in post‐myocardial infarction patients. European Journal of Clinical Investigation. 2007;37(6):454-62. https://doi.org/10.1111/j.1365-2362.2007.01805.x
24. Galvao TF, Matos KC, Brum PC, Negrao CE, da Luz PL, Chagas ACP. Cardioprotection conferred by exercise training is blunted by blockade of the opioid system. Clinics. 2011;66(1):151-7. https://doi.org/10.1590/s1807-59322011000100026
25. Shukla SK, Sharma SB, Singh UR. β-Adrenoreceptor agonist isoproterenol alters oxidative status, inflammatory signaling, injury markers and apoptotic cell death in myocardium of rats. Indian Journal of Clinical Biochemistry. 2015;30:27-34. https://doi.org/10.1007/s12291-013-0401-5
26. Xu X, Zhao W, Lao S, Wilson BS, Erikson JM, Zhang JQ. Effects of exercise and L-arginine on ventricular remodeling and oxidative stress. Medicine and Science in Sports and Exercise. 2010;42(2):346. https://doi.org/10.1249/mss.0b013e3181b2e899
27. Leite GAA, Sanabria M, Cavariani MM, Anselmo‐Franci JA, Pinheiro PFF, Domeniconi RF, et al. Lower sperm quality and testicular and epididymal structural impairment in adult rats exposed to rosuvastatin during prepuberty. Journal of Applied Toxicology. 2018;38(6):914-29. https://doi.org/10.1002/jat.3599
28. Gorzi A, Rajabi H, Azad A, Hedayati M. Effect of concurrent, strength and endurance training on hormones, lipids and inflammatory characteristics of untrained men. Iranian Journal of Endocrinology and Metabolism. 2012;13(6):614-20. [In Persian].
29. Asadi M, Rahmani M, Nasiri E, Kalantari-Hesari A, Khosravi-Sadr M, Ezzatifar M. Histomorphometric and histologic effect of endurance swimming on the testis of adult wistar rats. Journal of Applied Exercise Physiology. 2020;16(31):59-70. [In Persian].
30. Manna I, Jana K, Samanta P. Effect of different intensities of swimming exercise on testicular oxidative stress and reproductive dysfunction in mature male albino Wistar rats. Indian Journal of Experimental Biology. 2004;42:816-822. https://doi.org/10.1139/h04-013
31. Ergün A, Köse S, Aydos K, Ata A, Avci A. Correlation of seminal parameters with serum lipid profile and sex hormones. Archives of Andrology. 2007;53(1):21-3. https://doi.org/10.1080/01485010600888961
32. Sciorio R, Tramontano L, Adel M, Fleming S. Decrease in sperm parameters in the 21st century: obesity, lifestyle, or environmental factors? an updated narrative review. Journal of Personalized Medicine. 2024;14(2):198. https://doi.org/10.3390/jpm14020198
33. Pakpahan C, Rezano A, Margiana R, Amanda B, Agustinus A, Darmadi D. The association between lipid serum and semen parameters: a systematic review. Reproductive Sciences. 2023;30(3):761-71. https://doi.org/10.1007/s43032-022-01040-8
34. Jay R, Sturley R, Stirling C, McGarrigle H, Katz M, Reckless J, et al. Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia. British Journal of Clinical Pharmacology. 1991;32(4):417-22. https://doi.org/10.1111/j.1365-2125.1991.tb03924.x
35. LEON AS, SANCHEZ OA. Response of blood lipids to exercise training alone or combined with dietary intervention. Medicine & Science in Sports & Exercise. 2001;33(6):S502-S15. https://doi.org/10.1097/00005768-200106001-00021
36. La Vignera S, Condorelli RA, Vicari E, Calogero AE. Statins and erectile dysfunction: a critical summary of current evidence. Journal of Andrology. 2012;33(4):552-8. https://doi.org/10.2164/jandrol.111.015230
37. Omolaoye TS, Cyril AC, Radhakrishnan R, Rawat SS, Karuvantevida N, du Plessis SS. The Effect of Statins on Male Reproductive Parameters: A Mechanism Involving Dysregulation of Gonadal Hormone Receptors and TRPV1. International Journal of Molecular Sciences. 2023;24(11):9221. https://doi.org/10.3390/ijms24119221
38. e Silva PV, Borges CdS, Rosa JdL, Pacheco TL, Figueiredo TM, Leite GAA, et al. Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats. Journal of Applied Toxicology. 2020;40(7):947-64. https://doi.org/10.1016/j.toxlet.2016.07.569
39. S du Plessis S, Kashou A, Vaamonde D, Agarwal A. Is there a link between exercise and male factor infertility? The Open Reproductive Science Journal. 2011;3(1).
40. Hackney A. Effects of endurance exercise on the reproductive system of men: the “exercise-hypogonadal male condition”. Journal of Endocrinological Investigation. 2008;31:932-8. https://doi.org/10.1007/bf03346444
41. Cumming DC, Wheeler GD, McColl EM. The effects of exercise on reproductive function in men. Sports Medicine. 1989;7:1-17. https://doi.org/10.2165/00007256-198907010-00001
42. Hyyppä MT, Kronholm E, Virtanen A, Leino A, Jula A. Does simvastatin affect mood and steroid hormone levels in hypercholesterolemic men? A randomized double-blind trial. Psychoneuroendocrinology. 2003;28(2):181-94. https://doi.org/10.1016/s0306-4530(02)00014-8
43. Stanworth RD, Kapoor D, Channer KS, Jones TH. Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes. Diabetes Care. 2009;32(4):541-6. https://doi.org/10.2337/dc08-1183
44. Shuhaili MFRMA, Samsudin IN, Stanslas J, Hasan S, Thambiah SC. Effects of different types of statins on lipid profile: a perspective on Asians. International Journal of Endocrinology and Metabolism. 2017;15(2). https://doi.org/10.5812/ijem.43319
45. Hackney AC. The male reproductive system and endurance exercise. Medicine and Science in Sports and Exercise. 1996;28(2):180-9. https://doi.org/10.1097/00005768-199602000-00005
46. Safarinejad MR, Azma K, Kolahi AA. The effects of intensive, long-term treadmill running on reproductive hormones, hypothalamus-pituitary-testis axis, and semen quality: a randomized controlled study. Journal of Endocrinology. 2009;200(3):259. https://doi.org/10.1677/joe-08-0477
Ouf AM, Mohammed AF, Hanafi SM. Effect of Atorvastatin on the testes of adult male albino rats and the possible protective effect of vitamin E. Al-Azhar Assiut Medical Journal. 2015;13(4):100-18.