اثر محافظتی ملاتونین بر هورمون‌های محور هیپوفیز- بیضه و فرایند اسپرماتوژنز در موش سوری نژاد Balb/c بالغ القاء شده با سرترالین

نویسندگان

1 کارشناسی شد زیست شناسی، دانشکده علوم پایه، دانشگاه پیام نور مرکز اصفهان، اصفهان، ایران

2 دانشیار گروه آموزشی زیست شناسی، دانشکده علوم پایه، دانشگاه پیام نور مرکز اصفهان، اصفهان، ایران

3 استادیار گروه آموزشی زیست شناسی، دانشکده علوم پایه، دانشگاه پیام نور مرکز اصفهان، اصفهان، ایران

چکیده

مقدمه: سرترالین بر عملکرد جنسی و باروری اثر گذار است. ملاتونین یک آنتی‌اکسیدان قوی و دارای پتانسیل بالا جهت خنثی‌سازی سموم دارویی می‌باشد. هدف از انجام این مطالعه، بررسی اثرات ملاتونین بر تغییرات بافت  بیضه موش‌های سوری و تغییرات محور هیپوفیز- بیضه به دنبال تزریق داخل صفاقی سرترالین بود.
روش کار: 40 سر موش‌ نر سوری به صورت تصادفی به 5 گروه تقسیم شدند: گروه کنترل، شاهد(دریافت کننده سرترالین 50 میلی گرم بر کیلوگرم وزن بدن، روزانه به مدت دو هفته) وگروه های تجربی 1، 2 و 3، که ملاتونین با سه دوز مختلف به ترتیب (5، 10و 15 میلی گرم بر کیلوگرم وزن بدن) به صورت تزریق داخل صفاقی تیمار می شدند. گروه های تجربی، ملاتونین و سرترالین را به ترتیب به صورت یک روز درمیان و روزانه، به مدت 2 هفته  دریافت می کردند. پس از 15 روز، میزان هورمون های جنسی با خون گیری مستقیم از قلب حیوان و هیستولوژی بیضه مورد بررسی قرار گرفت.
یافته‌ها: موش های دریافت کننده سرترالین در مقایسه با گروه کنترل، کاهش معنی دار در میزان هورمون های تستوسترون، FSH و LH (P˂0.01) و فرایند اسپرماتوژنز(P˂0.001) مشاهده گردید. ملاتونین در گروه های تجربی 2 و 3، اثرات مضر سرترالین بر هورمون ها (P˂0.01)، بافت بیضه و کیفیت بلوغ اسپرماتوژنز را بهبود بخشید (p<0.05).
 نتیجه ­گیری: تجویز ملاتونین به صورت وابسته به دوز باعث کاهش عوارض ناشی از سرترالین بر میانگین سطح سرمی هورمون های جنسی و تعداد سلول های دودمان اسپرماتوژنز در موش سوری نر می شود.
 

کلیدواژه‌ها

عنوان مقاله [English]

Protective effect of melatonin on pituitary- gonadal axis hormones and spermatogenesis in sertraline-induced adult Balb/c mice

نویسندگان [English]

  • Mahmoud Goudarzi 1
  • Ali Asghar Pilehvarian 2
  • Akbar Karimi 3

1 MSc in Animal Biology, Faculty of Natural Sciences, University of Payame Noor, Esfahan, Iran

2 Associate Professor, Department of Biology, Faculty of Sciences, Payam-e-Noor University, Esfahan, Iran

3 Assistant Professor, Department of Biology, Faculty of Sciences, Payam-e-Noor University, Esfahan, Iran

چکیده [English]

Introduction: Sertraline affects sexual function and fertility. Melatonin is a powerful antioxidant with the ability to neutralize medical toxins. The present study was an attempt to investigate the effects of melatonin on testicle tissue changes and pituitary- gonadal axis changes occurring in in Balb/c rats following intraperitoneally administered sertraline.
Materials and Methods: 40 male Balb / c mice were randomly assigned into 5 groups: control, sham (receiving sertraline at dose of 50 mg/kg body weight per day for two weeks) and experimental groups 1, 2 and 3 in which melatonin
was intraperitoneally administered at 5, 10 and 15 mg/kg body weight respectively). The experimental groups received melatonin and sertraline every other day and every day for 2 weeks, respectively. 15 days later, gonadal hormones through direct cardiac blood sampling and testicular histology were assessed.
Results: Sertraline-receiving rats, compared to the control group rats, showed a significant decrease in the levels
of testosterone, FSH and LH (P˂0.01) and spermatogenesis (P˂0.001) compared to the control group. In experimental groups 2 and 3, Melatonin improved the adverse effects of sertraline on hormones (P˂0.01), gonadal tissue and spermatogenesis maturation process (P˂0.05).
Conclusion: Dose-dependent Melatonin administration can reduce the sertraline-induced effects on the mean serum
levels of gonadal hormones and the number of spermatogenic lineage cells in Balb /c male mice.

کلیدواژه‌ها [English]

  • Melatonin
  • Testis
  • Sertraline
  • infertility
  • Balb / c mice
[1] Mohammadi F, Nikzad H, Taherian A, Amini Mahabadi J, Salehi M. Effects of herbal medicine on male infertility. Anatomical sciences. 2013; 10: 3-16. [2] Vahidi S, Ardalan A, Mohammad K. The prevalence of primary infertility in the Islamic Republic of Iran in the years 2004. Asia pac J Public Health. 2009; 21: 287-93. [3] Gertsik L, Poland RE, Bresse C, Rapaport MH.Omega-3 fatty acid augmentation of citalopram treatment for patients with major depressive disorder. J Clin Psychopharmacol. 2012 Feb; 32(1):61-4. doi: 10.1097/JCP.0b013e31823f3b5f. Cited in PubMed; PMID: 22198441. [4] Kheirabad GR,Yousefian Z, Ghasem Ni, Zamani M, Maracy MR. [Comparison of Citalopram and Metacognitive Therapy on Depression in Patients with Major Depressive Disorder.] Journal of Isfahan Medical School, November2017; Vol.35, No.447:1242-1246. (Farsi). [5] Bazrafshan M.R, Manssori A. [survey of anxiety in infertile women referred to larestan gynecological clinics]. Iran J Reproduct Med (IJRM) 2010; 8 (1): 60. (Farsi). [6] Bazrafshan MR, Mahmoudi Rad AR. [The relationship between women's anxiety during pregnancy and labor outcomes in Larestan hospitals] Quarterly Sci Res J Aligoudarz Nursing Faculty (mandish) 2010; 1 (1): 1-12. (Farsi). [7] Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJ, Zisapel N, et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol 2008; 85: 335- 53.2008.04.001. [8] Henigberg N, Aj Sm, Hrabac P, Kalemberp, Rados Metal Changes In Brain Metaolits Measured With Magneti E Resonans Espectros Copy In Antidepressant Respanders Cith Comorbid Major Depression And Posttraumatic Steress- Disorder. Col Antro[Ol 2010: 35 (Suppl 1): 145-8. doi: 10.1016/j.pnpbp.2010.07.008. [9] Göçmez SS, Utkan T, Ulak G, et al. Effects of long-term treatment with fluoxetine and venlafaxine on rat isolated vas deferens. Auton Autacoid Pharmacol. 2010 Jul;30(3):197-202. doi: 10.1111/j.1474- 8673.2010.00456.x. Cited in PubMed; PMID: 20565446. [10] AmandaHolck, Owen MWolkowitz, Sindy HMellon, Victor IReus, J CraigNelson, ÅsaWestrin, DanielLindqvist. Plasma serotonin levels are associated with antidepressant response to SSRIs. Journal of Affective Disorders, Volume 250, 1 May 2019, Pages 65-70. DOI:10.1016/j.jad.2019.02.063 , PMID: 30831543 [11] Wei SM, Yan ZZ, Zhou J. Involvement of reactive oxygen species and TATA box-binding protein-related factor 2 in testicular torsion/detorsion-induced injury. Urology 2013; 81:e9-14. doi: 10.1016/j.urology.2012.09.021. PMID: 23374846 [12] Reiter RJ, Rosales-Corra SA, Manchester LC, Tan DX. Peripheral reproductive organ health and melatonin: ready for prime time. Int J Mol Sci 2013; 14:7231–72. DOI: 10.3390/ijms14047231. PMID: 23549263 [13] Stutz G, Zamudio J, Santillán ME, Vincenti L, de Cuneo MF, Ruiz RD. The effect of alcohol, tobacco, and aspirin consumption on seminal quality among healthy young men. Arch Environ Health 2004; 59(11):548-52. doi: 10.1080/00039890409603432. DOI: 10.1080/00039890409603432. PMID: 16599001 [14] Polat A, Emre MH. Influence of melatonin and acetylsalicylic acid on lipid peroxidation and antioxidant enzyme activities in gastric mucosa. J Gastroenterol 2006; 4:507-508. doi: 10.1007/s10616-013-9594-y. DOI: 10.1007/s00535-006-1837-7. PMID: 16799898 [15] Hussein MR, Abu-Dief EE, Abou El-Ghait AT, Adly MA, Abdelraheem MH.[Morphological evaluation of the radioprotective effects of melatonin against X-ray-induced early and acute testis damage in Albino rats]: an animal model. Int J Exp Pathol 2006; 87(3):237-50. (Farsi). [16] Chunjin Li, Xu Zhou, College of Animal Sciences, Jilin University, 5333 Xi'an Avenue, Changchun, Jilin Province 130062, PR China Melatonin and male reproduction.Clinica chimica Acta 446(2015); 175-180. [17] Ozlem Y, Ozbek E. Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats. Fertil Stril.2009; 92:1124-32. doi: 10.1016/j.fertnstert.2008.07.1758. DOI: 10.1016/j.fertnstert.2008.07.1758. PMID: 18829000 [18] Miller E,Walezak A, Majsterek I, Kedoziora J.Melatonin reduces oxidative stress in the erythrocytes of multiple sclerosis patients with secondary progressive clinical course. J Neuroimmunol 2013; 257:97-101. DOI: 10.1016/j.jneuroim.2013.02.012. PMID: 23517928 [19] Lagana AS , Rossetti P , Sapia F , Chiofalo B , Buscema M , Valenti G , Rapisarda AMC , Vitale SG . Evidence-based and patient-oriented inositol treatment in polycystic ovary yndrome: changing the perspective of the disease . Int J Endocrinol Metab 2017 ; 15 : e43695 . DOI: 10.5812/ijem.43695 PMID: 28835764 [20] Porpora MG, Tomao F, Manganaro L, Yazdanian D, Fuggetta E, Piccioni MG, Benedetti Panici P, Benagiano G. Impaired uterine artery flow associated with the presence of ovarian endometrioma: preliminary results of a prospective study. J Ovarian Res. 2014 Jan 8;7:1. doi: 10.1186/1757-2215-7-1. PMID: 24401654 [21] Goldstein CA , Lanham MS , Smith YR , O’Brien LM . Sleep in women undergoing in vitro ertilization: a pilot study . Sleep Med 2017 ; 32 : 105 – 113. DOI: 10.1016/j.sleep.2016.12.007 . PMID: 28366321 [22] Shavi Fernando, Sarah Nichole Biggs, Rosemary Sylvia Claire Horne, Beverley Vollenhoven, Nicholas Lolatgis, Nicole Hope, Melissa Wong, Mark Lawrence, Anthony Lawrence, Chris Russell, Kenneth Leong, Philip Thomas, Luk Rombauts, Euan Morrison Wallace. The impact of melatonin on the sleep patterns of women undergoing IVF: a double blind RCT Human eproduction Open, Volume 2017, Issue 4, 2017, hox027, https://doi.org/10.1093/hropen/hox027. Published: 06 January 2018. . PMID: 23374846 [23] Pasha l,Mokhtari M, Khatam saz S, Shariati M. Protective effect of sertraline on the pituitary-testis axis hormones in mature and process of spermatogenesis in mature a rats.2017 sep; 10(4):13-14 [24] Mohamadghasemi F, Faghani M, Khajehjahromi S, Bahadori M Nasiri E, Hemadi M. [Effect of Melatonin on proliferative activity and apoptosis in spermatogenic cells in mouse under chemotherapy.] Journal of Reproduction & Contraception 2010; 21(2): 79-94. (Farsi). [25] Bazrafshan M.R, Manssori A. [study of distress among infertile women referred to larestan ynecological clinics). Iran J Reproduct Med (IJRM) 2010; 8 (1): 71. (Farsi). [26] Tanrikut C, Feldman AS, Altemus M, et al. Adverse effect of paroxetine on sperm. Fertil Steril. 2010 Aug;94(3):1021 doi: 10.1016/j.fertnstert.2009.04.039. Epub 2009 Jun 10. Cited in PubMed;PMID: 19515367. [27] Lau BW, Yau SY, Lee TM, et al. Effect of corticosterone and paroxetine on masculine mating behavior:Possible involvement of neurogenesis. J Sex Med 2011 May; 8 (5): 1390-403. doi: 10.1111/j.1743- 6109.2010.02081.x. Cited in PubMed; PMID: 20955318 [28] Aronson JK. Meyler's Side Effects of Drugs 16th Edition The International Encyclopedia of Adverse Drug Reactions and Interactions30th October 2015 Elsevier.2015.351-354 [29] Reiter RJ, Tan D-x, Manchester LC, Qi W. Biochemical reactivity of melatonin with reac- tive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys. 2001;34(2):237-56. Cited in PubMed; PMID: 11898866 [30] Matsushima Y, Terada K, Kamei C, Sugimoto Y. Sertraline inhibits nerve growth factor-induced neurite outgrowth in PC12 cells via a mechanism involving the sigma-1 receptor. Eur J Pharmacol. 2019 Mar 19;853:129-135. DOI: 10.1016/j.ejphar.2019.03.032. [31] Pacchierotti C, Iapichino S, Bossini L, Pieraccini F, Castrogiovanni P. Melatonin in psychiatric disorders: a review on the melatonin involvement in psychiatry. Front Neuroendocrinol. 2001; 22: 18-32. doi: 10.1006/frne.2000.0202.27. PMID: 11141317 [32] Tuunainen A, Kripke DF, Elliott JA, Assmus JD, Rex KM, Klauber MR, et al. Depression and endogenous melatonin in post-menopausal women. . J Affect Disord. 2002 May;69(1-3):149-58. Cited in PubMed; PMID: 12103461.28 [33] Téllez-Zenteno JF, Cardiel MH. Risk factors associated with depression in patients with type 2 diabetes mellitus. Arch Med Res. 2002 Jan-Feb;33(1):53-60. Cited in PubMed; PMID: 11825632.29 [34] . Sahna E, Türk G, Ceriba ş i AO, Yilmaz S, Yüce A, et al. Chemoprotective effect of melatonin against cisplatin-induced testicular toxicity in rats. J Pineal Res 2006; 41(1):21- 7.doi: 10.12691/jcrt-2-3-4.30. PMID: 16842537 [35] Mao A, Guo H, Liu Y, Wang F, Tang J, Liao S, Zhang Y, Sun C, Xia X, Zhang H. Exogenous melatonin modulates carbon ion radiation-induced immune dysfunction in mice. Toxicology. 2019 Apr 1;417:35-41. DOI: 10.1016/j.tox.2019.01.019. PMID: 30779955 [36] . Bodinat C, Guardiola-lemaitre B,Mocaer E, Renard P, Munoz C, Mhllan mj. Agomelatine, the first melatoner- gic antidepressant: discovery, characterization and de- velopment. Nat Rev Drug Discov. 2010; 9: 628- 42. doi: 10.1038/nrd3140.31 [37] Madsen MT1,2,3,4,5, Isbrand A6, Andersen UO7, Andersen LJ8, Taskiran M6, Simonsen E9,10, Gögenur I11,10. The effect of Melatonin on Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS): study protocol for a randomized controlled trial. Trials. 2017 Feb 23;18(1):81. doi: 10.1186/s13063-017-1806-x. Cited in PubMed; PMID: 28228148.32 [38] . Parlaktas BS, Ozyurt B, Ozyurt H, Tunc AT, Akbas A. Levels of oxidative stress parameters and the protective effects of melatonin in psychosis model rat testis. 2007.,Asian J Androl . doi: 10.1111/j.1745-7262.2008.00338.x.33. PMID: 18097523 [39] d'Istria M, Serino I, Izzo G, Ferrara D. De Rienzo G, Minucci S. Effects of melatonin treatment on Leydig cell activity in the testis of the frog Rana Esculata. Zygote. 2004 Nov;12(4):293-9. Cited in PubMed; PMID: 15751537.34 [40] Khaksara M, Oryana A, Sayyaria M, Rezabakhsh A, ahbarghazi R.. [ Protective effects of melatonin on long-term administration of fluoxetine in rats Experimental and Toxicologic]. Pathology 69 (2017); 564_ 574. 35(Farsi).