Avni KILIÇ, HACER UYANIKOĞLU, Adnan İNCEBIYIK

Rat Overinde İskemi-Reperfüzyon Üzerine N-Asetil Sistein ve Resveratrol'ün Koruyucu Etkisi

Amaç: Bu çalışmanın amacı, rat overinde iskemi-reperfüzyona bağlı doku hasarı üzerine N-asetil sistein ve resveratrol'ün etkisini değerlendirmektir.Yöntemler: 42 adet dişi Wistar rat temin edildi. Bu ratlar randomize bir şekilde 6 gruba eşit olarak bölündü (n=7). Oluşturulan gruplar; sham (S), torsiyon (T), torsiyon - detorsiyon (T - D), torsiyon - detorsiyon + salin (T - DT - S), torsiyon - detorsiyon + resveratrol (20 mg/kg) (T - DT - Res) ve torsiyon - detorsiyon + N-asetil sistein (150 mg/kg) (T - DT - NAC) şeklinde işlemlere tabi tutuldu. Sham grubu hariç diğer tüm gruplara iki saat boyunca ovaryan torsiyon işlemi uygulandı. Torsiyon grubu dışındaki diğer tüm gruplara 2 saat detorsiyon prosedürü uygulandı. Salin, resveratrol ve N-asetil sistein gruplarında yer alan ratlara; detorsiyon işleminden yarım saat önce intraperitoneal yoldan 2 ml serum fizyolojik, 20 mg/kg resveratrol ve 150 mg/kg N-asetil sistein uygulandı. Ardından tüm ratlardan oksidatif stres markerları ve tümör nekrotizan faktör alfa (TNF-?) düzeylerinin çalışılması için 2 ml kan örneği ile histolojik inceleme için torsiyone edilen overler çıkarıldı. Histopatolojik değişiklikler ödem, konjesyon, hemoraji, lökosit infiltrasyonu ve follikül dejenerasyonu şeklinde tanımlandı.Bulgular: Histopatolojik hasar skorlamasına göre en az hasar sham grubunda, en fazla ise torsiyon-detorsiyon grubunda olduğu görüldü (1,00±0,81, 11,00±1,15, p

Protective Effect of N-Acetylcystein and Resveratrol on Ischemia-Reperfusion Injury in Rat Ovary

Objective: The aim of this study is evaluating the protective activity of N-acetyl cysteine and resveratrol treatment against ischemia - reperfusion damage created experimentally in rat ovaries.Methods: 42 female Wistar rats were used in our study. Rats were separated randomly into six groups consisting of seven rats as sham, torsion, torsion- detorsion, torsiondetorsion+saline, torsion-detorsion+resveretrol (20 mg/kg) and torsion- detorsion+N-acetyl cysteine (150 mg/kg). Except Sham, ovarian torsion procedure was implemented to all other groups for 2 hours. Detorsion procedure was implemented to other groups for 2 hours, except the torsion group. Medications were given through intraperitoneal way half an hour before the detorsion procedure in saline (two milliliter), resveratrol (20 mg/kg) and N-acetyl cysteine (150 mg/kg) groups. Then, 2 ml of blood samples were drawn for markers of oxidative stress and tumour necrosis factor-alpha (TNF-?) work and the ovaries, which were torsioned for the histologic examination, were extracted from all rats. Edema, congestion, hemorrhage, leukocyte infiltration and degeneration of follicles were evaluated by histopathological examination. Results: According to histopathologic damage scores, the least damage was seen in sham group and the most damage was seen T-DT group (1.00±0.81 vs. 11.00±1.15, respectively; p<0.001). It was seen that resveratrol and N-acetyl cysteine treatments were effective in decreasing tissue damage (total damage score average 83.85±0.89 vs. 3.85±0.89, respectively; p<0.001), and on the other hand there was not any difference between resveratrol and N-acetyl cysteine treatments (p=0.966). Besides, it was determined that oxidative stress levels were higher in torsion - detorsion group and the resveratrol and N-acetyl cysteine treatment caused a significant decrease in oxidative stress levels. In additionally, the reductions of TNF-? levels were found to be equally effective in both drugs (8.68±1.88 vs. 7.85±2.08, p=0.968).Conclusion: Presented study showed that resveratrol and Nacetyl cysteine treatment can be effective in preventing tissue damage and oxidative stress, which is induced by ischemiareperfusion that is created in rat ovaries. On the other hand, no difference was found between the resveratrol and N-acetyl cysteine with regards to protective activity.

PDF

___

1. Hibbard LT. Adnexal torsion. Am J Obstet Gynecol 1985;152:456-461.
2. Mage G, Canis M, Mahnes H, et al. Laparoscopic management of adnexal torsion. A review of 35 cases. J Reprod Med 1989;34:520-524.
3. Porpora MG, Gomel V. The role of laparoscopy in the management of pelvic pain in women of reproductive age. Fertil Steril 1997;68:765-779.
4. Meyer JS, Harmon CM, Harty MP, et al. Ovarian torsion: Clinical and imaging presentation in children. J Pediatr Surg 1995;30:1433-1436.
5. Celik O, Turkoz Y, Hascalik S, et al. The protective effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in rat ovary. Eur J Obstet Gynecol Reprod Biol 2004;117:183-188.
6. Cakir Gungor AN, Gencer M, Karaca T, et al. The effect of hesperetin on ischemia-reperfusion injury in rat ovary. Arch Gynecol Obstet 2014;290:763-769.
7. Sahin FK, Cosar E, Koken G, et al. Protective effect of aprotinin on ischemia-reperfusion injury in rat ovary. J Obstet Gynaecol Res 2008;34:794-800.
8. Ustundag UV, Sahin S, Ak K,et al. The effects of tacrolimus on the activity and expression of tissue factor in the rat ovary with ischemia-reperfusion induced injury. Reprod Biol 2015;15:139-145.
9. Akdemir A, Sahin C, Erbas O, et al. Is ursodeoxycholic acid crucial for ischemia / reperfusion-induced ovarian injury in rat ovary? Arch Gynecol Obstet 2015;292:445-450.
10. Soleas GJ, Diamandis EP, Goldberg DM. Wine as a biological fluid: history, production, and role in disease prevention. J Clin Lab Anal 1997;11:287-313.
11. Cotgreave IA. N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv Pharmacol 1997;38:205-227.
12. Ergun Y, Koc A, Dolapcioglu K, et al. The protective effect of erythropoietin and dimethylsulfoxide on ischemia-reperfusion injury in rat ovary. Eur J Obstet Gynecol Reprod Biol 2010;152:186-190.
13. Eser A, Hizli D, Haltas H, et al. Effects of curcumin on ovarian ischemia- reperfusion injury in a rat model. Biomed Rep 2015;3:807-813.
14. Gedik E, Girgin S, Ozturk H, et al. Resveratrol attenuates oxidative stress and histological alterations induced by liver ischemia/reperfusion in rats. World J Gastroenterol 2008;14:7101- 7106.
15. Incebiyik A, Seker A, Camuzcuoglu H, et al. Does sildenafil have protective effects against ovarian ischemia-reperfusion injury in rats? Arch Gynecol Obstet 2015;291:1283-1288.
16. Abali R, Tasdemir N, Yuksel MA, et al. Protective effect of infliximab on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation. Eur J Obstet Gynecol Reprod Biol 2013;171:353-357.
17. Buyukhatipoglu H, Kirhan I, Vural M, et al. Oxidative stress increased in healthcare workers working 24-hour on-call shifts. Am J Med Sci 2010;340:462-467.
18. Sayyah-Melli M, Rashidi MR, Kaseb-Ganeh M, et al. The effect of erythropoietin against oxidative damage associated with reperfusion following ovarian detorsion. Eur J Obstet Gynecol Reprod Biol 2012;162:182-186.
19. Kara M, Daglioglu YK, Kuyucu Y, et al. The effect of edaravone on ischemia-reperfusion injury in rat ovary. Eur J Obstet Gynecol Reprod Biol 2012;162:197-202.
20. Maretta M, Bujdos M, Toth S Jr, et al. Alterations of epithelial layer after ischemic preconditioning of small intestine in rats. J Mol Histol 2012;43:171-178.
21. Bozkurt S, Arikan DC, Kurutas EB, et al. Selenium has a protective effect on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation. J Pediatr Surg 2012; 47:1735-1741.
22. Yılmaz H, Sahin S, Sayar N, et al. Effects of folic acid and Nacetylcysteine on plasma homocysteine levels and endothelial function in patients with coronary artery disease. Acta Cardiol 2007;62:579-585.
23. Millea PJ. N-Acetylcysteine: Multiple clinical applications. Am Fam Physician 2009;80:265-269.
24. Sun Z, Lasson A, Olanders K, et al. Gut barrier permeability, reticuloendothelial system function and protease inhibitor levels following intestinal ischaemia and reperfusion effects of pretreatment with N-acetyl-L-cysteine and indomethacin. Dig Liver Dis 2002;34:560-569.
25. Cay A, Alver A, Kucuk M, et al. the effects of N-aceyylcystein on antioxidant enzyme activities in experimental testicular torsion. J Surg Res 2006;131:199-203.
26. Smyrniotis V, Arkadopoulos N, Kostapanaqiotou G, et al. Attenuation of ischemic injury by N-acetylcysteine preconditioning of the liver. J Surg Res 2005;129:31-37.
27. Demir S, Inal-Erden M. Pentoxifylline and N-acetylcysteine in hepatic ischemia/reperfusion injury. Clin Chim Acta 1998;275:127-135.
28. Hoch JR, Stevens RP, Keller MP, et al. Recovery of neuromuscular function during reperfusion of the ischemic extremity: effect of mannitol and superoxide dismutase. Surgery 1991;110:656-662.
29. Bhalodia Y, Kanzariya N, Patel R, et al. Renoprotective activity of benincasa cerifera fruit extract on ischemia/reperfusioninduced renal damage in rat. Iran J Kidney Dis 2009;3:80-85.
30. Yuan GJ, Ma JC, Gong ZJ, et al. Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats. World J Gastroenterol 2005;11:1825-1828.
31. Huang SS, Tsai MC, Chih CL, et al. Resveratrol reduction of infarct size in Long-Evans rats subjected to focal cerebral ischemia. Life Sci 2001;69:1057-1065.
32. Hassan-Khabbar S, Cottart CH, Wendum D, et al. Postischemic treatment by trans-resveratrol in rat liver ischemia-reperfusion: a possible strategy in liver surgery. Liver Transpl 2008;14:451- 459