Clinical and Experimental Reproductive Medicine

  • 제51권3호
  • /
  • Pages.205-212
  • /
  • 2024
  • /
  • 2233-8233(pISSN)
  • /
  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지
DOI QR코드

DOI QR Code

Protective effects of Withania somnifera against cyclophosphamide-induced testicular damage in rats

  • Mehrana Jafari (Traditional and Complementary Medicine Research Center (TCMRC), Arak University of Medical Sciences) ;
  • Ahmad Akbari (Traditional and Complementary Medicine Research Center (TCMRC), Arak University of Medical Sciences) ;
  • Zeynab Esmailpour (Students Research Committee, Arak University of Medical Sciences) ;
  • Zahra Nadi (Students Research Committee, Arak University of Medical Sciences) ;
  • Maryam Baazm (Traditional and Complementary Medicine Research Center (TCMRC), Arak University of Medical Sciences)
  • 투고 : 2023.08.04
  • 심사 : 2023.12.26
  • 발행 : 2024.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective: Cyclophosphamide (CP) is an alkylating agent commonly used in cancer treatment. It is known to have detrimental effects on the reproductive system, including the potential to cause infertility. Recently, herbal remedies have gained traction as a complementary approach to addressing these side effects. In this study, our goal was to investigate whether the aqueous-alcoholic extract of Withania somnifera (WS) could mitigate the adverse impacts of CP on testicular tissue. Methods: Animals were randomly assigned to one of the following groups: control, WS (500 mg/kg), CP (100 mg/kg), CP+WS pre-treatment, and CP+WS post-treatment. WS was administered orally through gavage for 1 month. We assessed sperm parameters, testicular histopathology, and the expression of the Bax and Bcl2 genes in the experimental groups. Results: Sperm parameters (including count, viability, and motility), the number of spermatogonia, the seminiferous tubule diameter, and Bcl2 gene expression, significantly decreased after CP injection (p<0.05). Conversely, the number of immotile sperm and Bax gene expression significantly increased (p<0.05). Treatment with WS, especially when administered as a pre-treatment, ameliorated the sperm parameters, histological alterations, and the expression of apoptosis-related genes (p<0.05). Conclusion: The data suggest that WS may mitigate the detrimental effects of CP on testicular tissue by reducing apoptosis. Consequently, WS has the potential to be used as an adjunctive therapy to reduce the complications associated with CP treatment.

키워드

과제정보

This study was supported by the council of Arak University of Medical Sciences (grant number: 3812).

참고문헌

  1. Chiba K, Fujisawa M. Fertility preservation in men with cancer. Reprod Med Biol 2014;13:177-84. https://doi.org/10.1007/s12522-014-0180-6
  2. Liu X, Li Q, Wang Z, Liu F. Identification of abnormal protein expressions associated with mouse spermatogenesis induced by cyclophosphamide. J Cell Mol Med 2021;25:1624-32. https://doi.org/10.1111/jcmm.16263
  3. Kim SH, Lee IC, Baek HS, Moon C, Kim SH, Kim JC. Protective effect of diallyl disulfide on cyclophosphamide-induced testicular toxicity in rats. Lab Anim Res 2013;29:204-11. https://doi.org/10.5625/lar.2013.29.4.204
  4. Gajjar R, Miller SD, Meyers KE, Ginsberg JP. Fertility preservation in patients receiving cyclophosphamide therapy for renal disease. Pediatr Nephrol 2015;30:1099-106. https://doi.org/10.1007/s00467-014-2897-1
  5. Iorga A, Dara L, Kaplowitz N. Drug-induced liver injury: cascade of events leading to cell death, apoptosis or necrosis. Int J Mol Sci 2017;18:1018.
  6. Johnson SE, Ugolkov A, Haney CR, Bondarenko G, Li L, Waters EA, et al. Whole-body imaging of cell death provides a systemic, minimally invasive, dynamic, and near-real time indicator for chemotherapeutic drug toxicity. Clin Cancer Res 2019;25:1331-42. https://doi.org/10.1158/1078-0432.CCR-18-1846
  7. Ghobadi E, Moloudizargari M, Asghari MH, Abdollahi M. The mechanisms of cyclophosphamide-induced testicular toxicity and the protective agents. Expert Opin Drug Metab Toxicol 2017;13:525-36. https://doi.org/10.1080/17425255.2017.1277205
  8. Singh K, Bhori M, Kasu YA, Bhat G, Marar T. Antioxidants as precision weapons in war against cancer chemotherapy induced toxicity: exploring the armoury of obscurity. Saudi Pharm J 2018;26:177-90. https://doi.org/10.1016/j.jsps.2017.12.013
  9. Lee J, Jeong MI, Kim HR, Park H, Moon WK, Kim B. Plant extracts as possible agents for sequela of cancer therapies and cachexia. Antioxidants (Basel) 2020;9:836.
  10. Dar NJ, Hamid A, Ahmad M. Pharmacologic overview of Withania somnifera, the Indian Ginseng. Cell Mol Life Sci 2015;72:4445-60. https://doi.org/10.1007/s00018-015-2012-1
  11. Ahmed W, Mofed D, Zekri AR, El-Sayed N, Rahouma M, Sabet S. Antioxidant activity and apoptotic induction as mechanisms of action of Withania somnifera (Ashwagandha) against a hepatocellular carcinoma cell line. J Int Med Res 2018;46:1358-69. https://doi.org/10.1177/0300060517752022
  12. Tandon N, Yadav SS. Safety and clinical effectiveness of Withania Somnifera (Linn.) Dunal root in human ailments. J Ethnopharmacol 2020;255:112768.
  13. Mikulska P, Malinowska M, Ignacyk M, Szustowski P, Nowak J, Pesta K, et al. Ashwagandha (Withania somnifera): current research on the health-promoting activities. A narrative review. Pharmaceutics 2023;15:1057.
  14. Choudhary D, Bhattacharyya S, Joshi K. Body weight management in adults under chronic stress through treatment with ashwagandha root extract: a double-blind, randomized, placebo-controlled trial. J Evid Based Complementary Altern Med 2017;22:96-106. https://doi.org/10.1177/2156587216641830
  15. Kumar A, Kumar R, Rahman MS, Iqubal MA, Anand G, Niraj PK, et al. Phytoremedial effect of Withania somnifera against arsenic-induced testicular toxicity in Charles Foster rats. Avicenna J Phytomed 2015;5:355-64.
  16. Pavin NF, Izaguirry AP, Soares MB, Spiazzi CC, Mendez AS, Leivas FG, et al. Tribulus terrestris protects against male reproductive damage induced by cyclophosphamide in mice. Oxid Med Cell Longev 2018;2018:5758191.
  17. Kyathanahalli CN, Manjunath MJ. Oral supplementation of standardized extract of Withania somnifera protects against diabetes-induced testicular oxidative impairments in prepubertal rats. Protoplasma 2014;251:1021-9. https://doi.org/10.1007/s00709-014-0612-5
  18. Sengupta P, Agarwal A, Pogrebetskaya M, Roychoudhury S, Durairajanayagam D, Henkel R. Role of Withania somnifera (Ashwagandha) in the management of male infertility. Reprod Biomed Online 2018;36:311-26. https://doi.org/10.1016/j.rbmo.2017.11.007
  19. Bhargavan D, Deepa B, Shetty H, Krishna AP. The protective effect of Withania somnifera against oxidative damage caused by ethanol in the testes of adult male rats. Int J Basic Clin Pharmacol 2017;4:1104-8. https://doi.org/10.18203/2319-2003.ijbcp20151340
  20. Soleimani MZ, Jalali Mashayekhi F, Mousavi Hasanzade M, Baazm M. Alteration in CatSper1 and 2 genes expression, sperm parameters and testis histology in varicocelized rats. Int J Reprod Biomed 2018;16:183-90. https://doi.org/10.29252/ijrm.16.3.183
  21. Hemati U, Moshajari M, Jalali Mashayekhi F, Bayat M, Moslemi A, Baazm M. The effect of curcumin on NRF2/Keap1 signalling pathway in the epididymis of mouse experimental cryptorchidism. Andrologia 2022;54:e14532.
  22. Tajaddini S, Ebrahimi S, Behnam B, Bakhtiyari M, Joghataei MT, Abbasi M, et al. Antioxidant effect of manganese on the testis structure and sperm parameters of formalin-treated mice. Andrologia 2014;46:246-53. https://doi.org/10.1111/and.12069
  23. Babaei A, Kheradmand N, Baazm M, Nejati N, Khalatbari M. Protective effect of vitamin E on sperm parameters in rats infected with Candida albicans. Andrologia 2020;52:e13593.
  24. Fallah Asl H, Mashayekhi FJ, Bayat M, Habibi D, Zendedel A, Baazm M. Role of epididymis and testis in nuclear factor erythroid 2-related factor 2 signaling in mouse experimental cryptorchidism. Iran Red Crescent Med J 2019;21:e86806.
  25. Abd El Tawab AM, Shahin NN, AbdelMohsen MM. Protective effect of Satureja montana extract on cyclophosphamide-induced testicular injury in rats. Chem Biol Interact 2014;224:196-205. https://doi.org/10.1016/j.cbi.2014.11.001
  26. Durg S, Shivaram SB, Bavage S. Withania somnifera (Indian ginseng) in male infertility: an evidence-based systematic review and meta-analysis. Phytomedicine 2018;50:247-56. https://doi.org/10.1016/j.phymed.2017.11.011
  27. Paul S, Chakraborty S, Anand U, Dey S, Nandy S, Ghorai M, et al. Withania somnifera (L.) Dunal (Ashwagandha): a comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects. Biomed Pharmacother 2021;143:112175.
  28. Alzoubi KH, Al Hilo AS, Al-Balas QA, El-Salem K, El-Elimat T, Alali FQ. Withania somnifera root powder protects againist post-traumatic stress disorder-induced memory impairment. Mol Biol Rep 2019;46:4709-15. https://doi.org/10.1007/s11033-019-04915-3
  29. Hussain A, Aslam B, Muhammad F, Faisal MN, Kousar S, Mushtaq A, et al. Anti-arthritic activity of Ricinus communis L. and Withania somnifera L. extracts in adjuvant-induced arthritic rats via modulating inflammatory mediators and subsiding oxidative stress. Iran J Basic Med Sci 2021;24:951-61.
  30. Pawar P, Gilda S, Sharma S, Jagtap S, Paradkar A, Mahadik K, et al. Rectal gel application of Withania somnifera root extract expounds anti-inflammatory and muco-restorative activity in TNBS-induced inflammatory bowel disease. BMC Complement Altern Med 2011;11:34.
  31. Ambiye VR, Langade D, Dongre S, Aptikar P, Kulkarni M, Dongre A. Clinical evaluation of the spermatogenic activity of the root extract of Ashwagandha (Withania somnifera) in oligospermic males: a pilot study. Evid Based Complement Alternat Med 2013;2013:571420.
  32. Nasimi Doost Azgomi R, Nazemiyeh H, Sadeghi Bazargani H, Fazljou SM, Nejatbakhsh F, Moini Jazani A, et al. Comparative evaluation of the effects of Withania somnifera with pentoxifylline on the sperm parameters in idiopathic male infertility: a triple-blind randomised clinical trial. Andrologia 2018;50:e13041.
  33. Gupta A, Mahdi AA, Shukla KK, Ahmad MK, Bansal N, Sankhwar P, et al. Efficacy of Withania somnifera on seminal plasma metabolites of infertile males: a proton NMR study at 800 MHz. J Ethnopharmacol 2013;149:208-14. https://doi.org/10.1016/j.jep.2013.06.024
  34. Teixeira MYP, de Araujo COD. Effect of Withania somnifera in the treatment of male infertility: a literature review. J Med Plant Res 2019;13:473-9. https://doi.org/10.5897/JMPR2019.6823
  35. Wicinski M, Fajkiel-Madajczyk A, Kurant Z, Kurant D, Gryczka K, Falkowski M, et al. Can Ashwagandha benefit the endocrine system?: a review. Int J Mol Sci 2023;24:16513.
  36. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev 2000;5:334-46.
  37. Kumar P, Sharma R, Garg N. Withania somnifera: a magic plant targeting multiple pathways in cancer related inflammation. Phytomedicine 2022;101:154137.
  38. Nasimi Doost Azgomi R, Zomorrodi A, Nazemyieh H, Fazljou SM, Sadeghi Bazargani H, Nejatbakhsh F, et al. Effects of Withania somnifera on reproductive system: a systematic review of the available evidence. Biomed Res Int 2018;2018:4076430.
  39. Prakash J, Chouhan S, Yadav SK, Westfall S, Rai SN, Singh SP. Withania somnifera alleviates parkinsonian phenotypes by inhibiting apoptotic pathways in dopaminergic neurons. Neurochem Res 2014;39:2527-36. https://doi.org/10.1007/s11064-014-1443-7