Author(s):
Surekha D. Shetty, Laxminarayana Bairy K., Prasad AM, Satheesha Nayak B., Ashwini Aithal P.
Email(s):
ashwini.anat@gmail.com
DOI:
10.52711/0974-360X.2021.00674 
Address:
Surekha D. Shetty1, Laxminarayana Bairy K.2, Prasad AM1, Satheesha Nayak B.1, Ashwini Aithal P.1*
1Department of Anatomy, Melaka Manipal Medical College (Manipal Campus), Manipal Academy of Higher Education (MAHE) Manipal, Karnataka, India.
2RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras AI-Khaimah, UAE.
*Corresponding Author
Published In:
Volume - 14,
Issue - 7,
Year - 2021
ABSTRACT:
Background: Hormones play a vital role in initiating and maintenance of male reproductive or testicular function which includes the production of androgens and spermatozoa. Testosterone is essential for the initiation and maintenance of spermatogenesis. FSH is responsible for the stimulation of spermatogenesis. Semen analysis and hormone evaluation are essential parameters in the diagnosis of infertility in males. Objective: The aim of the present study is to evaluate the effect of sorafenib on FSH and intratesticular testosterone levels in male Swiss albino mice. Materials and Methods: The animals were segregated into control, positive control, and treatment groups (n=6). Treatment group received 25, 50 and 100 mg/kg body weight of sorafenib orally for seven consecutive days at intervals of 24 hours between two administrations. Positive control group received 100 mg/kg body weight of imatinib. The animals were sacrificed at the end of 1st, 2nd, 4th, 5th, 7th and 10th week after the last exposure to sorafenib. Results: The intratesticular testosterone level was significantly (P<0.05) reduced in treated groups and severe effect was observed on week 4th and 5th weeks. FSH level was increased significantly (P<0.05) in sorafenib treated groups of mice. Conclusion: The administration of sorafenib does affect testosterone and FSH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with sorafenib for advanced renal cell carcinoma, hepatocellular carcinoma and differentiated thyroid carcinoma.
Cite this article:
Surekha D. Shetty, Laxminarayana Bairy K., Prasad AM, Satheesha Nayak B., Ashwini Aithal P. Effect of Sorafenib on Sex Hormone Levels in Male Swiss Albino Mice. Research Journal of Pharmacy and Technology. 2021; 14(7):3883-8. doi: 10.52711/0974-360X.2021.00674
Cite(Electronic):
Surekha D. Shetty, Laxminarayana Bairy K., Prasad AM, Satheesha Nayak B., Ashwini Aithal P. Effect of Sorafenib on Sex Hormone Levels in Male Swiss Albino Mice. Research Journal of Pharmacy and Technology. 2021; 14(7):3883-8. doi: 10.52711/0974-360X.2021.00674 Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-7-71
REFERENCES:
1. Van Montfrans JM, Hoek A, Van Hooff MHA, De Koning CH, Tonch N, Lambalk CH. Predictive value of basal follicle stimulating hormone concentrations in a general sub fertility population. Fertility and Sterility. 2000; 74(1): 97-103.
2. Barth V, Schonfelder M. Dependence of serum hormones (T, FSH, LH) on morphometric testicular findings after chemo and radiotherapy in patients with malignant testicular tumors. Zent Allg Pathol. 1990; 136: 439-442.
3. Pont J, Albrecht W. Fertility after chemotherapy for testicular germ cell cancer. Fertil Steril. 1997; 68: 1-5.
4. Narayana K, Verghese S, Jacob SS. L-Ascorbic acid partially protects two cycles of cisplatin chemotherapy- induced testis damage and oligoastheno- teratospermia in a mouse model. Exp Toxicol Pathol. 2009; 61(6): 553-563.
5. Turk G, Ates S, Ahin A, Sonmez M, Osman C¸ Eribas A, et al. Improvement of cisplatin-induced injuries to sperm quality, the oxidant antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril. 2008; 89(5): 1474-1481.
6. Pakarainen T, Zhang FP, Makela S, Poutanen M, Huhtaniemi I. Testosterone Replacement Therapy Induces Spermatogenesis and Partially Restores Fertility in Luteinizing Hormone Receptor Knockout Mice. Endocrinology. 2005; 146(2): 596–606.
7. Sharpe R.M., Fraser H.M, Ratnasooriya, WD. Assessment of the role of Leydig cell products other than testosterone in spermatogenesis and fertility in adult rats. Int. J. Androl. 1988; 11: 507- 523.
8. Assennato G, Paci C, Baser ME, Molinini R, Candela RG, Altamura BM, et al. Sperm count suppression without endocrine dysfunction in lead-exposed men. Arch Environ Health. 1987; 42: 124-127.
9. Walker WH, Cheng J. FSH and testosterone signaling in Sertoli cells in Reproduction. Reproduction and Fertility. 2005; 130(1): 15-28.
10. Nieschlag E, Simoni M, Gromoll J, Weinbauer GF. Role of FSH in the regulation of spermatogenesis: clinical aspects. Clin Endocrinol (Oxf). 1999; 51(2): 139-46
11. De-Krester DM. Endocrinology of male infertility. Brit Med Bullet. 1979; 35: 187-192.
12. Wang, C., Iranmanesh, A. and Berman, N. Comparative pharmacokinetics of three doses of percutaneous dihydro-testosterone gel in healthy elderly men—a Clinical Research Center Study. J. Clin. Endocrinol. Metab. 1998; 83: 2749- 2757.
13. Cameron, D.F., Muffly, K.E. and Nazian, S.J. Reduced testosterone during puberty results in a midspermeiogenic lesion, Proc. Soc. Exp. Biol. Med. 1993; 202; 457-464.
14. Wyrobek, A., Gordon, L., Bukhart, J.G., Francis, M.W., Kapp, R.W., Letz, G., Malling, H.V., Topham JC, Whorton MD. On evaluation of the mouse sperm morphology test and other sperm tests in non-human mammals. Mutation Research. 1983; 115: 1-72.
15. Reddy, Y.V., Reddy, P.S., Shivalingam, M.R. and Gamini, C.P. Dose dependent alteration in epididymal sperm count of cisplatin or carboplatin treated male Wistar rats. J. Pharm. Sci. Res. 2009; 4: 167-172.
16. Zabul, J., Mierzejewski, W. and Rogoza, A. Usefulness of examining gonadotropin hormones and testosterone in men with abnormal semen. Ginekol-pol. 1994; 65(2): 71-74.
17. Anderson, R.A., Wallace, E.M., Groome. N.P, Bellis, A.J. and Wu,F.C.W. Physiological relationships between inhibin B, follicle stimulating hormone secretion and spermatogenesis in normal men and response to gonadotrophin suppression by exogenous testosterone. Hum. Reprod. 1997; 12: 746-7.
18. Tucker WE Jr. Preclinical toxicology profile of acyclovir: an overview. Am J Med. 1982; 73(1): 27-30.
19. Thomson AB, Campbell AJ, Irvine DC, Anderson RA, Kelnar CJ, Wallace WH. Semen quality and spermatozoal DNA integrity in survivors of childhood cancer: a case-control study. Lancet. 2002; 360: 361-367.
20. Santos AM, Ferraz MR, Teixeira CV, Sampaio FJ, Da Fonte RC: Effects of under nutrition on serum and testicular testosterone levels and sexual function in adult rats. Horm Metab Res. 2004; 36(1): 27-33.
21. Nithya R, Elango V. Pesticide Effect in Male Hormones and Antioxidant Status in Male Albino Rats. J Acad Indus Res. 2015; 4(4): 140-143.
22. Nurmio M, Toppari J, Zaman F, Andersson AM, Paranko J, Soder O, et al. Inhibition of tyrosine kinases PDGER and C-Kit by imatinib mesylate interferes with postnatal testicular development in the rat. Int J Androl. 2007; 30: 366-376.
23. Show MD, Folmer JS, Anway MD, Zirkin BR. Testicular expression and distribution of the rat Bcl-2 modifying factor (Bmf) in response to reduced intratesticular testosterone. Reprod Biol. 2004; 70: 1153-1161.
24. Zhang J, Lia Z, Qiea M, Zheng R, Shetty J, Wanga J. Sodium fluoride and sulfur dioxide affected male reproduction by disturbing blood-testis barrier in mice. Food Chem Toxicol. 2016; 94: 103-111.
25. Debnath D, Mandal TK. Study of quinalphos (an environmental oestrogenic insecticide) formulation (Ekalux 25 E.C.)-induced damage of the testicular tissues and antioxidant defence systems in sprague-dawley albino rats. J Appl Toxicol. 2000; 20(3): 197-204.
26. Ayala A, Munoz MF, Arguelles S. Lipid peroxidation: production, metabolism, and signalling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014; 2014: 360438.
27. Kata FS. Effectt of Ciisplatiin drug on sperm characterizes, spermatogenesis and sex hormones levels of male mice. J Basrah Res. 2013; 39(2): 112-124.
28. Niakani A, Farrokhi F, Hasanzadeh S. Decapeptyl ameliorates cyclophosphamide-induced reproductive toxicity in male Balb/C mice: histomorphometric, stereologic and hormonal evidences. Iran J Reprod Med. 2013; 11(10): 791-800.
29. Sun J, Cao Y, Zhang X, Zhao Q, Bao E, Lv Y, et al. Melamine negatively affects testosterone synthesis in mice. Res Vet Sci. 2016; 109: 135-141.
30. Kumar V, Chakraborty A, Kural MR, Roy P. Alteration of testicular steroidogenesis and histopathology of reproductive system in male rats treated with triclosan. Reprod Toxicol. 2009; 27: 177-185.
31. Aydiner A, Aytekin Y, Topuz E. Effect of Cisplatin on testicular tissue and the Leydig cell- pituitary axis. J Oncol. 1997; 54: 74-78.
32. Maines MD, Sluss PM, Mumtaz I. Cis-Platinum-mediated decrease in serum testosterone is associated with depression of luteinizing hormone receptors and cytochrome P-450scc in rat testis. J Endocrinol. 1990; 126; 2398-2406.
33. Elangovan N, Chiou T, Tzeng W, Chu S. Cyclophosphamide treatment causes impairment of sperm and its fertilizing ability in mice. J Toxicol. 2006; 222: 60-70.
34. Malarvizhi D, Mathur PP. Effects of cisplatin on testicular functions in rats. Indian J Exp Biol. 1996; 34; 995-998.
35. Brennan J, Tilmann C, Capel B. Pdgfr-alpha mediates testis cord organization and fetal Leydig cell development in the XY gonad. Genes Dev. 2003; 17: 800-810.
36. Gnessi L, Basciani S, Mariani S, Arizzi M, Spera G, Wang C, et al. Leydig cell loss and spermatogenic arrest in platelet derived growth factor (PDGF) Adeficient: mice. J Cell Biol 2000; 149: 1019-1026.
37. Basciani S, Mariani S, Arizzi M, Ulisse S, Rucci N, Jannini EA, et al. Expression of platelet-derived growth factor-A (PDGF-A), PDGF-B, and PDGF receptor-alpha and -beta during human testicular development and disease. J Clin Endocrinol Metab. 2002; 87: 2310-2319.
38. Khan MR, Ahmed D. Protective effects of Degera muricata (L.) Mart. On testis against oxidative stress of carbon tetrachloride in rat. Food Chem Toxicol. 2009; 47: 1393-1399.
39. Hägerkvist R, Sandler S, Mokhtari D, Welsh N. Amelioration of diabetes by imatinib mesylate (Gleevec): Role of beta-cell NF-kappa B activation and anti-apoptotic preconditioning. FASEB J 2007; 21: 618-628.
40. Blanco-Rodriguez J, Martinez-Garcia C. Apoptosis pattern by oestradiol treatment of the seminiferous epithelium of the adult rat. J. Reprod. Fertil. 1997; 110: 61-70.
41. Merino G, Carranza-Lira S. Seman characteristics, endocrine profile and testicular biopsies of interfile men of different ages. Arch Androl. 1995; 35(3): 219-244.
42. Bergmann M, Behre HM, Nieschlag E. Serum FSH and testicular morphology in male infertility. Clin Endocrinol. 1994; 40:133-136.
43. Soares PM, Borba EF, Bonfa E, Hallak J, Correa AL, Silva CA. Gonad evaluation in male systemic lupus erythematosus. Arthritis Rheum. 2007; 56: 2352-2361.
44. Huhtaniemi I, Toppari J. Endocrine, paracrine and autocrine regulation of testicular steroidogenesis. Adv Exp Med Biol. 1995; 377: 33-54.
45. Ghabili K, Shoja MM, Golzari SE, Ansarin K. Serum testosterone level and semen indices in sulfur mustard exposed men: comment on “sperm chromatin structure assay analysis of Iranian mustard gas casualties: a long-term outlook”. Curr Urol. 2012; 6: 112.
46. Panahi Y, Ghanei M, Ghabili K, Ansarin K, Aslanabadi S, Poursaleh Z, et al. Acute and chronic pathological effects of sulfur mustard on genitourinary system and male fertility. Urol J. 2013; 10: 837-846.
47. Jalali AS, Hasanzadeh S. Crataegus monogyna fruit aqueous extract as a protective agent against doxorubicin-induced reproductive toxicity in male rats. Avicenna Journal of Phytomedicine. 2013; 3(2): 159-170.
48. Bustos-Obregon E, Croxatto H. Gametogenesis, A. Alfredo Pérez Sánchez, Editor, Ginecologia, Editorial Mediterraneo, Chile. 2003: 60-75.
49. Mohandes Z, Shariati M. The Effect of Venustat on Sex Hormones and Testicular Tissue in Adult Rats. J Appl Environ Biol Sci. 2016; 6(1): 113-117.
50. Van Thiel DH, Sherins RJ, Myers GH Jr, and Devita VT Jr. Evidence for a specific seminiferous tubular factor affecting follicle - stimulating hormone secretion in man. Journal of Clinical Investigation. 1972; 51(4): 1009-1019.