Testis Torsiyonuna bağlı gelişen Testiste Fibrozis mast hücre stabilizatörü olan Ketotifen ile önlenebilir mi?
Abstract
Amaç: İnfertilite kliniklerinde, inmemiş testis nedeni ile testis atrofisi gelişen olgu biopsilerinde testiste normalde olmayan mast hücreleri tespit edilmiştir. Buna bağlı olarak, testis atrofisine giden fibrozis sürecinde mast hücrelerinin katkısı olduğu düşünülmüştür. Çalışmamızda amaç, rat testis torsiyon- detorsiyon modelinde testiste gelişen fibrozisin önlemesi amacıyla bir mast hücre stabilizatörü olan ketotifenin etkinliğinin araştırılmasıdır.
Materyal- Metod: Otuz rat, üç eşit gruba ayrıldı. Grup A’ da testis yapıları gubernakulumdan ayrılıp torsiyon yapmadan yerine kondu (sham). Grup B’ de sağ testiküler torsiyon oluşturulup dört saat sonra detorsiyone edildi. Grup C’ de dört saatlik torsiyonu takiben detorsiyon yapılan ratlara ketotifen (1 mg/kg/gün, oral yolla, birinci günden itibaren üç haftaya kadar verildi). Ratlar, üç hafta sonra anestezi altında sakrifiye edilerek testiküler fibrozis gelişimi yönünden değerlendirildi. Histopatolojik değerlendirme Johnsen skoru kullanılarak yapıldı.
Sonuçlar: Johnsen scorlarının median değerleri grup A, B, C’ de sırasıyla 9,9, 3,7 ve 8,4 bulundu. Grup C (ketotifen) diğer gruplar ile karşılaştırıldığında, Johnsen skoru yüksekliği istatistiksel olarak anlamlı bulundu (p< 0.05) (Kruskall-Wallis). İkili karşılaştırma yapıldığında gruplar arasında anlamlı farklar olduğu saptandı: grup A-B; p=0,0001, grup B-C; p=0,039, grup A-C; p=0,006).
Tartışma: Bir testis torsiyon-detorsiyon rat modelinde, ketotifenin bir mast hücre stabilizatörü olarak testis fibrozisine karşı önleyici etkinliği olduğunu saptadık. Torsiyon- detorsiyon sonrasında kalan testiste mast hücre ekspresyonu ve germ hücre aktivitesini ilişkilendiren klinik çalışmalar yol gösterici olacaktır.
Supporting Institution
Ankara Çocuk Sağlığı ve Hastalıkları Hematoloji Onkoloji Eğitim Araştırma Hastanesi Eğitim Fonu
References
- 1. Wynn, T.A. and T.R. Ramalingam, Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med, 2012. 18(7): p. 1028-40.
- 2. Mechlin, C.W., et al., Mast cell numbers negatively correlate with fibrosis in cryptorchid testes. J Pediatr Urol, 2014. 10(3): p. 527-31.
- 3. Bradding, P. and G. Pejler, The controversial role of mast cells in fibrosis. Immunol Rev, 2018. 282(1): p. 198-231.
- 4. Acer-Demir, T., 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(4): p. 672-680.
- 5. Moreno, D., et al., Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord. Asian J Androl, 2020. 22(1): p. 112-117.
- 6. AZILI, M.N., et al., Effects of Captopril and Ketotifen on Protecting Against Renal Scarring Due to Pyelonephritis Injury.
- 7. Welter, H., et al., Angiotensin II regulates testicular peritubular cell function via AT1 receptor: a specific situation in male infertility. Mol Cell Endocrinol, 2014. 393(1-2): p. 171-8.
- 8. Garbuzenko, E., 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(2): p. 237-46.
- 9. Spinnler, K., et al., Human tryptase cleaves pro-nerve growth factor (pro-NGF): hints of local, mast cell-dependent regulation of NGF/pro-NGF action. J Biol Chem, 2011. 286(36): p. 31707-13.
Can Testicular Fibrosis Due to Testicular Torsion Be Prevented with Ketotifen As A Mast Cell Stabilizer?
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.
References
- 1. Wynn, T.A. and T.R. Ramalingam, Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med, 2012. 18(7): p. 1028-40.
- 2. Mechlin, C.W., et al., Mast cell numbers negatively correlate with fibrosis in cryptorchid testes. J Pediatr Urol, 2014. 10(3): p. 527-31.
- 3. Bradding, P. and G. Pejler, The controversial role of mast cells in fibrosis. Immunol Rev, 2018. 282(1): p. 198-231.
- 4. Acer-Demir, T., 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(4): p. 672-680.
- 5. Moreno, D., et al., Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord. Asian J Androl, 2020. 22(1): p. 112-117.
- 6. AZILI, M.N., et al., Effects of Captopril and Ketotifen on Protecting Against Renal Scarring Due to Pyelonephritis Injury.
- 7. Welter, H., et al., Angiotensin II regulates testicular peritubular cell function via AT1 receptor: a specific situation in male infertility. Mol Cell Endocrinol, 2014. 393(1-2): p. 171-8.
- 8. Garbuzenko, E., 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(2): p. 237-46.
- 9. Spinnler, K., et al., Human tryptase cleaves pro-nerve growth factor (pro-NGF): hints of local, mast cell-dependent regulation of NGF/pro-NGF action. J Biol Chem, 2011. 286(36): p. 31707-13.
Details
| Primary Language | English |
|---|---|
| Subjects | Surgery |
| Journal Section | ORIGINAL ARTICLES |
| Authors | |
| Publication Date | May 25, 2021 |
| Submission Date | April 14, 2021 |
| Published in Issue | Year 2021 Volume: 15 Issue: 3 |
The publication language of Turkish Journal of Pediatric Disease is English.
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