اثرات درمانی عصاره آبی- الکلی برگ اسفناج آبی در مقابل سمیت ناشی از مصرف بوسولفان بر پارامترهای باروری در موش صحرایی نر؛ یک مطالعه کارآزمایی بالینی تصادفی شاهددار

نوع مقاله : اصیل پژوهشی

نویسندگان

1 دانشیار گروه علوم تشریح، دانشکده پزشکی، دانشگاه علوم پزشکی کرمانشاه، کرمانشاه، ایران.

2 دانشیار گروه پرستاری، پژوهشکده سلامت، دانشکده پرستاری، دانشگاه علوم پزشکی کرمانشاه، کرمانشاه، ایران.

3 دانشجوی دکترای علوم تشریح، دانشکده پزشکی، دانشگاه علوم پزشکی کرمانشاه، کرمانشاه، ایران.

چکیده

مقدمه: داروی بوسولفان جهت معالجه سرطان، به‌علت خواص اکسیداسیونی و تولید رادیکال­های آزاد سبب اختلال در پارامترهای باروری مردانه می­شود و برگ گیاه اسفناج آبی دارای خواص آنتی‌اکسیدانی است. مطالعه حاضر با هدف ارزیابی اثر برگ اسفناج آبی بر بهبود آسیب‌های دستگاه تناسلی نر ناشی از بوسولفان انجام شد.
روش­کار: این مطالعه کارآزمایی بالینی تصادفی شاهددار در سال 1398 بر روی 48 موش صحرایی نر نژاد ویستار انجام شد. نمونه‌ها در 8 گروه شامل: نرمال سالین، بوسولفان، عصاره برگ اسفناج آبی با دوزهای 250، 500 و 1000 میلی‌گرم/کیلوگرم و عصاره + بوسولفان قرار گرفتند. تیمار روزانه و طی 2 ماه به‌صورت داخل صفاقی انجام شد. پارامترهای اسپرم با استفاده از تکنیک­های رنگ‌سنجی و توسط میکروسکوپ نوری، سطح مالون دی‌آلدهید بیضه توسط اسپکتروفتومتری، ظرفیت آنتی‌اکسیدان تام و تستوسترون با روش الایزا و ارتفاع لایه سمینی فروس از طریق میکروسکوپ نوری و نرم‌افزار موتیک اندازه‌گیری شد. تجزیه و تحلیل داده‌ها با استفاده از نرم‌افزار آماری SPSS (نسخه 20) و آزمون‌ تکمیلی توکی انجام شد. میزان p کمتر از 05/0 معنی‌دار در نظر گرفته شد.
یافته­ها: مقادیر پارامترهای اسپرم، هورمون تستوسترون و ظرفیت آنتی‌اکسیدان تام در گروه کنترل منفی نسبت به کنترل مثبت به‌طور معنی‌داری کاهش یافت (01/0>p). تیمار توسط عصاره و عصاره+ بوسولفان در تمامی دوزها، به‌طور معنی­داری موجب افزایش تمامی پارامترهای ذکر شده نسبت به گروه کنترل منفی شد (01/0>p). در پارامترهای بررسی شده در گروه­ عصاره به‌تنهایی، تغییر معنی‌داری نسبت به گروه کنترل مثبت مشاهده نشد (05/0<p).
نتیجه­گیری: عصاره برگ اسفناج کیفیت اسپرم را افزایش داده و اثرات سوء بوسولفان را بر روی پارامترهای تولید مثلی نر بهبود می­بخشد.

کلیدواژه‌ها


عنوان مقاله [English]

Therapeutic effects of hydro-alcoholic extract of water spinach leaf against toxicity following Busulfan administration on fertility parameters in male rats; A randomized controlled clinical trial study

نویسندگان [English]

  • Mohammad Reza Salahshoor 1
  • Shiva Roshankhah 1
  • Amir Jalali 2
  • Amir Abdolmaleki 3
1 Associate professor, Department of Anatomical Sciences, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
2 Associate professor, Department of Nursing, Research Institute for Health, School of Nursing, Kermanshah University of Medical Sciences, Kermanshah, Iran.
3 PhD candidate of Anatomical Sciences, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
چکیده [English]

Introduction: Busulfan drug for cancer treatment, due to the oxidation properties and free radicals production, causes disturbance on male fertility parameters, and leaves water spinach plant have antioxidant features. The current study was aimed to evaluate the effect of water spinach leaf on recovery of male genital injuries caused by Busulfan.
Methods: This randomized controlled clinical trial was performed on 48 male rats of Wistar race in 2019. The specimens were divided into 8 groups including; normal saline, Busulfan, water spinach leaf extract with doses of 250, 500, and 1000 mg/kg, extract + Busulfan. Daily treatment for 2 months was administered intraperitoneally. Sperm parameters by colorimetric techniques and light microscopy, level of testis malondialdehyde by spectrophotometry, total antioxidant capacity and testosterone by ELISA method, and height of germinal layer through optical microscopy and Motic software were evaluated. Data analysis was applied by SPSS software (version 20) and Tukey post-hoc test. P< 0.05 were considered statistically significant.
Results:The values of sperm parameters, testosterone hormone, and total antioxidant capacity were significantly decreased in negative control group than positive control (P < 0.01). Treatment by extract and extract + Busulfan in all doses significantly increased whole mentioned parameters compared to the negative control group (P < 0.01). In evaluated parameters in extract group alone, no significant changes were observed compared to the positive control group (P > 0.05).
Conclusion: Leaf extract of water spinach plant increases the sperm quality and improves the Busulfan-induced adverse effects on male reproductive parameters.

کلیدواژه‌ها [English]

  • Water spinach
  • Fertility
  • Busulfan
  • Clinical trial
  1. Solomon R, Shvartsur R, Azab AN. The Association Between Psychotropic Drug Use and Fertility Problems Among Male Subjects. J Psychiatr Pract 2019; 25(1):22‐33.
  2. Liu FJ, Dong WY, Zhao H, Shi XH, Zhang YL. Effect of molybdenum on reproductive function of male mice treated with busulfan. Theriogenology 2019; 126:49‐54.
  3. Ganjalikhan Hakemi S, Sharififar F, Haghpanah T, Babaee A, Eftekhar-Vaghefi SH. The Effects of Olive Leaf Extract on The Testis, Sperm Quality and Testicular Germ Cell Apoptosis in Male Rats Exposed to Busulfan. Int J Fertil Steril 2019; 13(1):57‐65.
  4. Abofoul-Azab M, Lunenfeld E, Levitas E, et al. Identification of Premeiotic, Meiotic, and Postmeiotic Cells in Testicular Biopsies Without Sperm from Sertoli Cell-Only Syndrome Patients. Int J Mol Sci 2019; 20(3):470.
  5. Dehghani F, Sotoude N, Bordbar H, Panjeshahin MR, Karbalay-Doust S. The use of platelet-rich plasma (PRP) to improve structural impairment of rat testis induced by busulfan. Platelets 2019; 30(4):513‐520.
  6. Jalilvand N, Hosseini M, Beheshti F, Ebrahimzadeh-Bideskan A. Protective effect of PPARγ agonist pioglitazone, on testicular tissue and sperm parameters in hypothyroid rats. Toxin Reviews 2019; 24:1-10.
  7. Honaramooz A, Behboodi E, Hausler CL, et al. Depletion of endogenous germ cells in male pigs and goats in preparation for germ cell transplantation. J Androl 2005; 26(6):698‐705.
  8. Li B, He X, Zhuang M, et al. Melatonin Ameliorates Busulfan-Induced Spermatogonial Stem Cell Oxidative Apoptosis in Mouse Testes. Antioxid Redox Signal 2018; 28(5):385‐400.
  9. Vafaei A, Mohammadi S, Fazel A, Soukhtanloo M, Pour AM, Beheshti F. Effects of carob (Ceratonia siliqua) on sperm quality, testicular structure, testosterone level and oxidative stress in busulfan-induced infertile mice. Pharmaceutical Sciences 2018; 24(2):104-111.
  10. Jalili C, Kamani M, Roshankhah S, Sadeghi H, Salahshoor MR. Effect of Falcaria vulgaris extracts on sperm parameters in diabetic rats. Andrologia 2018; 50(10):e13130.
  11. Salahshoor MR, Haghjoo M, Roshankhah S, Makalani F, Jalili C. Effect of Thymoquinone on Reproductive Parameter in Morphine-treated Male Mice. Adv Biomed Res 2018; 7:18.
  12. Salahshoor MR, Khazaei M, Jalili C, Keivan M. Crocin Improves Damage Induced by Nicotine on A Number of Reproductive Parameters in Male Mice. Int J Fertil Steril 2016; 10(1):71‐78.
  13. Roshankhah Sh, Jalili C, Salahshoor MR. Protective effects of Petroselinum crispum on ischemia/reperfusion-induced acute kidney injury in rats. Physiol Pharmacol 2019; 23(2):129-139.
  14. Roshankhah Sh, Jalili C, Salahshoor MR. The effects of Petroselinum crispum extract on milk production parameters in female rats. Scientific Journal of Kurdistan University of Medical Sciences 2019; 24(1):11-23.
  15. Kitayama M, Tisarum R, Theerawitaya C, Samphumphung T, Takagaki M, Kirdmanee C, et al. Regulation on anthocyanins, α-tocopherol and calcium in two water spinach (Ipomoea aquatica) cultivars by NaCl salt elicitor. Scientia Horticulturae 2019; 249:390-400.
  16. Bokolo B, Adikwu E. Ethanolic leaf extract of Ipomoea aquatica Forsk abrogates cisplatin-induced kidney damage in albino rats. J Nephropharmacol 2019; 8(1):58-67.
  17. Kurade MB, Xiong JQ, Govindwar SP, Roh HS, Saratale GD, Jeon BH, et al. Uptake and biodegradation of emerging contaminant sulfamethoxazole from aqueous phase using Ipomoea aquatica. Chemosphere 2019; 225:696-704.
  18. Dewanjee S, Dua TK, Khanra R, et al. Water Spinach, Ipomoea aquatic (Convolvulaceae), Ameliorates Lead Toxicity by Inhibiting Oxidative Stress and Apoptosis [published correction appears in PLoS One. 2015;10(11):e0143766]. PLoS One 2015; 10(10):e0139831. Published 2015 Oct 16.
  19. Malakar C, Choudhury PPN. Pharmacological potentiality and medicinal uses of Ipomoea aquatica Forsk: a review. Asian J Pharm Clin Res 2015; 8(2):60-3.
  20. Umar K, Muhammad M, Sani N, Muhammad S, Umar M. Comparative Study of Antioxidant Activities of the Leaves and Stem of Ipomoea aquatica Forsk (Water Spinach). Nigerian Journal of Basic and Applied Sciences 2015; 23(1):81-4.
  21. Ibrahim MH, Abas NA, Zahra SM. Impact of Salinity Stress on Germination of Water Spinach (Ipomoea aquatica). Annual Research & Review in Biology 2019: 1-12.
  22. Qu N, Itoh M, Sakabe K. Effects of chemotherapy and radiotherapy on spermatogenesis: The role of testicular immunology. International journal of molecular sciences 2019; 20(4):957.
  23. Ghasemzadeh A, Nouri M, Sedghiani M, Yousefzadeh S, Fadaei Fouladi R. Effects of Pentoxifylline on In Vitro Sperm Motility and Viability of Infertile Males with Oligoasthenospermia. Iran J Obstet Gynecol Infertil 2013; 15(38):1-6.
  24. Ahemen T, Abu AH, Orakaanya TT. Sperm quality and testicular morphometry of rabbits fed dietary levels of water spinach (Ipomoea aquatica) leaf meal. Agriculture and biology journal of north America 2013; 4(3):352-357.
  25. Alkiyumi SS, Abdullah MA, Alrashdi AS, Salama SM, Abdelwahab SI, Hadi AH. Ipomoea aquatica extract shows protective action against thioacetamide-induced hepatotoxicity. Molecules 2012; 17(5):6146‐6155. Published 2012 May 22.
  26. Selvakumar E, Prahalathan C, Mythili Y, Varalakshmi P. Protective effect of DL-alpha-lipoic acid in cyclophosphamide induced oxidative injury in rat testis. Reprod Toxicol 2004; 19(2):163‐167.
  27. Potnuri AG, Allakonda L, Lahkar M. Crocin attenuates cyclophosphamide induced testicular toxicity by preserving glutathione redox system. Biomed Pharmacother 2018 ;101:174‐180.
  28. Olejnik J, Suchowerska N, Herrid M, Jackson M, Hinch G, Hill J. Spermatogonia survival in young ram lambs following irradiation, Busulfan or thermal treatment. Small ruminant research 2018; 166:22-7.
  29. Aitken RJ, Baker MA. Oxidative stress, sperm survival and fertility control. Mol Cell Endocrinol 2006; 250(1-2):66‐69.
  30. Moloody M, Shahrooz R, Razi M, Zarei L, Mohammadi V. The Effect of CoQ10 on Testicular Tissue in Rats Treating with Busulfan: Sperm Quality and Histological Changes. Iranian Journal of Veterinary Surgery 2018; 13(1):29-38.
  31. Bahmanpour S, Namavar Jahromi B, Koohpeyma F, Keshavarz M, Bakhtari A. Effects of Different Doses and Time-Dependency of Busulfan on Testes Parameters and Spermatogenesis in a Rat Model: A Quantitative Stereological Study. Journal of Advanced Medical Sciences and Applied Technologies 2017; 3(3):155-62.
  32. Bar-Shira Maymon B, Yogev L, Marks A, Hauser R, Botchan A, Yavetz H. Sertoli cell inactivation by cytotoxic damage to the human testis after cancer chemotherapy. Fertil Steril 2004; 81(5):1391‐1394.
  33. Saenphet K, Saenphet S, Intamong J, Nakas T, Buncharoen W. Acute toxicity and histopathological changes in livers of frog tadpoles (Hoplobatrachus rugulosus) exposed to bioinsecticides derived from Azadirachta indica A. Juss., Stemona curtisii Hook. F., and Mammea siamensis. Comparative Clinical Pathology 2018; 27(4):939-46.
  34. Zheng Y, Hu G, Wu W, et al. Reshaping fecal gut microbiota composition by growing with Polygonum cuspidatum, Houttuynia cordata, and Ipomoea aquatica. Can J Microbiol 2019; 65(7):522‐529.
  35. Abu A, Ameh M, Iheukwuemere F. Semen quality of Nigerian local cocks treated with human menopausal gonadotropin (Pergonal®). Livestock Research for Rural Development 2006; 18(3):44.
  36. Zhao Y, Zhang S. PGAM1 knockdown is associated with busulfan‑induced hypospermatogenesis and spermatogenic cell apoptosis. Mol Med Rep 2019; 19(4):2497‐2502.
  37. Vahdati A, Fathi AR, Nasimi P, Saki G. Busulfan induces apoptotic and cytotoxic effects on testis and epididymal sperm of adult male mouse following low dose treatment. Int J Bio 2015; 5:70-78.
  38. Guvvala PR, Sellappan S, Parameswaraiah RJ. Impact of arsenic(V) on testicular oxidative stress and sperm functional attributes in Swiss albino mice. Environ Sci Pollut Res Int 2016; 23(18):18200‐18210.