Abstract
Background: In infertility clinics, biopsies taken from undescended atrophic testicles showed increased mast cells which are not found in normal testis. So, it was thought that mast cells could have a contributing effect on fibrosis leading to testicular atrophy. Our aim of the study is to investigate the efficacy of ketotifen, which is a mast cell stabilizer, on the prevention of testicular fibrosis in a testicular torsion-detorsion rat model.
Materials and Methods: Thirty rats were divided into three equal groups, each consisting of ten animals. In group A; the testicular tissues were only separated from the gubernaculum without torsion (Sham). In group B, detorsion was performed after four hours of testicular torsion in the right testes. In group C, after four hours of right testicular torsion and detorsion, the rats were taken ketotifen as a medical treatment (1 mg/kg/day, orally started on the first day, continued for three weeks). The rats were sacrificed under anesthesia, three weeks after surgery to determine testicular fibrosis. Histopathologic evaluation was performed with Johnsen's score in both testes as a control evaluation.
Results: According to Johnsen score, median values were found 9.9 in group A; 3.7 in group B, and 8.4 in group C. Johnsen score was found significantly high in group C (with ketotifen) when compared with the other groups (p< 0.05). When we made a pairwise comparison, we found a significant difference between the group's A and B (p=0.0001), the group’s B and C; (p=0.039), and the group’s A and C (p=0.006).
Conclusion: We found that ketotifen had a preventing effect against testicular fibrosis as a mast cell stabilizer in the testis torsion-detorsion rat model.
Keywords: Ketotifen, Mast cell stabilizer, Testis torsion, Testicular fibrosis
References
- Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 2012;181028-40.
- Mechlin CW, Levesque J, Feustel P, Kogan BA. Mast cell numbers negatively correlate with fibrosis in cryptorchid testes. J Pediatr Urol 2014;10:527-31.
- Bradding P, Pejler G. The controversial role of mast cells in fibrosis. Immunol Rev 2018;282:198-231.
- Acer-Demir T, Mammadov M, Öcbe P, Çoruhlu A, Coşkun D, Nazik Y, et al. The long term effects of intrascrotal low dose and high dose N-acetylcysteine on testis damage in rat model of testicular torsion. J Pediatr Surg 2020;55:672-80.
- Azılı MN, Karakuş E, Şenaylı A, Tiryaki Ht. Effects of Captopril and Ketotifen on Protecting Against Renal Scarring Due to Pyelonephritis Injury. Turkish J Pediatr Dis 2019; 6: 475-80.
- Welter H, Huber A, Lauf S, et al. Angiotensin II regulates testicular peritubular cell function via AT1 receptor: a specific situation in male infertility. Mol Cell Endocrinol 2014;393:171-8.
- Garbuzenko E, Nagler A, Pickholtz D, P Gillery, R Reich, F-X Maquart, et al. Human mast cells stimulate fibroblast proliferation, collagen synthesis and lattice contraction: a direct role for mast cells in skin fibrosis. Clin Exp Allergy 2002;32:237-46.
- Moreno D, Sobarzo CM, Lustig L, Rodriguez Pena MG, Guazzone VA. Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord. Asian J Androl 2020;22:112-7.
- Akgur FM, Kilinc K, Tanyel FC, Buyukpamukcu N, Hicsonmez A. Ipsilateral and contralateral testicular biochemical acute changes after unilateral testicular torsion and detorsion. Urology 1994;44:413-8.
- Anderson MJ, Dunn JK, Lipshultz LI, Coburn M. Semen quality and endocrine parameters after acute testicular torsion. J Urol 1992;147:1545-50.
- Widgerow AD. Ischemia-reperfusion injury: influencing the microcirculatory and cellular environment. Ann Plast Surg2014;72:253-60.
- Dubois R, Dodat H. Acute scrotum in the child. Arch Pediatr 1998;5:916-22.
- Kutluhan MA, Urkmez A, Sahin A, Topaktas R, Gumrukcu G, Verit A. Predictive value of ischaemia-modified albumin in spermatogenesis in an experimental testicular torsion model. Andrologia 2020;52:e13471.
Copyright and license
Copyright © 2021 The Author(s). This is an open access article distributed under the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.