DENEYSEL TESTİS TORSİYONU SONRASI İSKEMİ/REPERFÜSYON HASARINDA İLOPROST VE DÜŞÜK DOZ METOTREKSAT’IN KORUYUCU ETKİSİ

Year 2017, , 131 - 138, 18.12.2017

Ercan Yuvanç , Devrim Tuğlu , Üçler Kısa Önder Bozdoğan , Ertan Batislam Erdal Yılmaz

https://doi.org/10.24938/kutfd.336398

Abstract

Amaç: Testis torsiyonunda cerrahi olarak
detorsiyone edilen testiste gelişen iskemi/reperfüzyon (I/R) hasarı üzerine
İloprost ve düşük doz Metotreksat’ın koruyucu etkilerini araştırmak.

Gereç ve Yöntem: Ratlar rastgele 4 gruba ayrıldı.
Grup 1 (sham), Grup 2 = İskemi/Reperfüzyon, ilaç verilmedi. Grup 3 =
İskemi/Reperfüzyon + İloprost (10 µg/kg) ve Grup 4 = İskemi/Reperfüzyon + Düşük
doz Metotreksat (6 mg/kg). Torsiyon/iskemi ve detorsiyon/reperfüzyon süreleri
4’er saat olarak belirlenmiştir. Medikasyonlar intraperitoneal yolla testis
torsiyonunu takiben 3. saatte verilmiştir. Her 4 grupta işlemin başlangıcından
8 saat sonra detorsiyone sağ testis çıkarılmıştır.

Bulgular: Çalışmamızda, iloprost ve düşük doz
metotreksat verilmesinin total antioksidan kapasiteyi (TAK) istatistiksel
olarak anlamlı arttırdığını, oksidan kapasite markırı olan total oksidan kapasite
(TOK) ve oksidatif stres indeks oranını (OSI) ise istatistiksel olarak anlamlı
düzeyde azalttığını belirledik. İskemi-reperfüzyon grubu testislerde testis
grupları arasında Johnsen skorlama sistemine göre istatistiksel farklılık
saptanmadı.

Sonuç: Bizim düşüncemize göre iloprost ve
düşük doz metotreksat tedavisi, testis örneklerinde antioksidan aktiviteyi
arttırmış, oksidan aktiviteyi de baskılamıştır. Ancak, histopatolojik
incelemede ve spermatogenes skorlarında bir değişime neden olmamıştır.

Keywords

Testis torsiyonu, detorsiyon, antioksidan, iskemi/reperfüzyon, iloprost, düşük doz metotreksat

The Protective Effect of Iloprost and Low-Dose Methotrexate on Testicular Ischemia/Reperfusion Injury in an Experimental Model

Abstract

Objective: To investigate the protective effects of iloprost and
low-dose methotrexate on ischemia/reperfusion (I/R) injury in surgically
detorsed testicular torsion.

Material and Methods: Rats were randomly divided into 4 groups: Group 1 (sham),
Group 2: Only testicular I/R; Group 3: I/R+iloprost (10 μg/kg) and Group 4:
I/R+low dose metotrexate (6 mg/kg). Torsion / ischemia and detorsion /
reperfusion times were determined as 4 hours. Medications were given
intraperitoneally at 3 hours following onset of testicular torsion. Detorsioned
right testises were removed 8 hours after the begining of the procedure in all
4 groups.

Results: In our study, we found that administration of iloprost and
metotrexate significantly increased total antioxidant capacity (TAC) while
reducing total oxidant statüs (TOS) and oxidative stress index (OSI) levels
significantly. No statistically significant difference was found for testicles
in I/R groups according to the Johnsen scoring system.

Conclusion: Admnistration of iloprost and low dose methotrexate treatment
increased antioxidant activity in testicular samples while suppressing oxidant
activity. However, there was no change in histopathological examination and
spermatogenesis scores.

Keywords

Testis torsion, detorsion, antioxidant, ischemia/reperfusion, iloprost, methotrexate

References

• 1. Sheweita SA, Tilmisany AM, Al-Sawaf H. Mechanisms of male infertility: role of antioxidants. Curr Drug Metab. 2005;6:495-501.
• 2. Prillaman HM, Turner TT. Rescue of testicular function after acute experimental torsion. J Urol. 1997;157:340-345.
• 3. Akgür FM, Kilinç K, Tanyel FC, et al. Ipsilateral and contralateral testicular biochemical acute changes after unilateral testicular torsion and detorsion. Urology. 1994;44:413-418.
• 4. Akgür FM, Kilinç K, Aktug˘ T. Reperfusion injury after detorsion of unilateral testicular torsion. Urol Res. 1993;21:395-399.
• 5. Grant SM, GoaKL. Iloprost: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in peripheral vascular disease, myocardial ischemia, and extracorporeal circulation procedures. Drugs 1992;43:889–924.
• 6. Kisch-Wedel H, KemmingG, MeisnerF, FlondorM, Bruhn S, KoehlerC, etal. Effect of prostaglandin I2 analogues on left ventricular diastolic function invivo. Eur J Pharmacol. 2005;517:208–16.
• 7. Moncada S. Biological importance of prostacyclin. Br J Pharmacol. 1982;76:3–31.
• 8. Bozkurt AK. Alpha-tocopherol (vitaminE) and iloprost attenuate reperfusion injury in skeletal muscle ischemia/reperfusion injury. J Cardiovasc Surg. 2002;43:693–6.
• 9. Emrecan B, Tulukoglu E, Bozok S, Kestelli M, Onem G, Kupelioglu A, etal. Effects of iloprost and pentoxifylline on renal ischemia-reperfusion in rabbit model. Eur J Med Res. 2006;31:295–9.
• 10. Yozai K, Shikata K, Sasaki M, et al: Methotrexate prevents renal injury in experimental diabetic rats via anti-inflammatory actions. J Am Soc Nephrol. 2005;16:3326-3338.
• 11. Nash RA, Pineiro LA, Storb R, Deeg HJ, Fitzsimmons WE, Furlong T, Hansen JA, Gooley T, Maher RM, Martin P, McSweeney PA, Sullivan KM, Anasetti C, Fay JW: FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors. Blood 1996;88: 3634–3641.
• 12. Weinblatt ME, Maier AL, Fraser PA, Coblyn JS: Longterm prospective study of methotrexate in rheumatoid arthritis: Conclusion after 132 months of therapy. J Rheumatol. 1998;25: 238–242.
• 13. Asanuma H, Sanada S, Ogai A, Minamino T, Takashima S, Asakura M, Ogita H, Shinozaki Y, Mori H, Node K, Tomoike H, Hori M, Kitakaze M. Methotrexate and MX-68, a new derivative of methotrexate, limit infarct size via adenosine-dependent mechanisms in canine hearts. J Cardiovasc Pharmacol. 2004;Apr;43(4):574-9.
• 14. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37:112–9.
• 15. Erel O. A new automated colorimetric method for measuring total oxidant status.Clin Biochem. 2005;38:1103–11.
• 16. Johnsen SG, Testicular biopsy score count–a method for registration of spermatogenesis in human testes: normal values and results of 335 hypogonadal males. Hormones 1970;1:2-25.
• 17. Wei SM, Yan ZZ, Zhou J. Protective effect of rutin on testicular ishemia–reperfusion injury. J Pediatr Surg. 2011;46:1419–24.
• 18. Gezici A, Öztürk H, Büyükbayram H, et al. Effects of gabexate mesilate on ischemia–reperfusion-induced testicular injury in rats. Pediatr Surg Int. 2006;22:435–41.
• 19. Akgür FM, Kılınç K, Aktuğ T. Reperfusion injury after detorsion of unilateral testicular torsion. Urol Res. 1993;21:395–9.
• 20. Belkin M, Wright JG, Hobson RW. Iloprost infusion decreases skeletal muscle ischemia-reperfusion injury. J Vasc Surg. 1990;11:77.
• 21. Canacankatan N, Sucu N, Aytaçoğlu B, et al. Affirmative effectsof ıloprost on apoptosis during ıschemia-reperfusion ınjury in kidney as a distant organ. Renal Fail. 2012;34:111–118.
• 22. Della Bella S, Molteni M, Mocellin C, Fumagalli S, Bonara P, Scorza R. Novel mode of action of iloprost: in vitro downregulation of endothelial cell adhesion molecules. Prostaglandins Other Lipid Mediat. 2001;65:73.
• 23. Johannes T, Ince C, Klingel K, et al. Iloprost preserves renal oxygenation and restores kidney function in endotoxemia-related acute renal failure in therat. Crit Care Med. 2009;37:1423–1432.
• 24. Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 1993;92:2675-82.
• 25. Chan ES, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res 2002;4:266-73.
• 26. Montesinos MC, Takedachi M, Thompson LF, Wilder TF, Fernández P, Cronstein BN. The antiinflammatory mechanism of methotrexate depends on extracellular conversion of adenine nucleotides to adenosine by ecto-5’-nucleotidase: findings in a study of ecto-5’-nucleotidase gene-deficient mice. Arthritis Rheum 2007;56:1440-5.