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-α) 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<0,001, p<0,001, sırasıyla). Resveratrol ile N-asetil sistein tedavisinin doku hasarını azaltmada etkili olduğu (total hasar skoru ortalaması: (83,85±0,89 ve 3,85±0,89 sırasıyla; p<0,001), buna karşın her iki ilaç arasında histopatolojik hasarın azaltılmasında anlamlı bir farklılığın olmadığı görüldü (p=0,966). Torsiyon-detorsiyon grubunda oksidatif stres düzeylerinin daha yüksek olduğu, resveratrol ile N-asetil sistein tedavisinin ise oksidatif stres düzeylerinde belirgin bir azalmaya neden olduğu saptandı. Ayrıca TNF-alfa düzeylerinin ilaç verilen gruplarda anlamlı ölçüde azaldığı tespit edildi (7,85±2,08 ve 8,68±1,88 sırasıyla; p<0,001). Buna karşın TNF-α düzeylerini azaltmada her iki ilacın da eşit etkinlikte olduğu gözlendi (8,68±1,88 ve 7,85±2,08, sırasıyla; p=0,968). Sonuç: Resveratrol ve NAC tedavisinin ovaryan reperfüzyona bağlı gelişen oksidatif stres ve doku hasarının azaltılmasında etkili olabileceği düşünülmektedir. Her iki ilaç arasında koruyucu etkinlik açısından bir fark bulunmadı.

Anahtar Kelimeler:

İskemi-reperfüzyon, over, N-asetilsistein, resveratrol

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, torsion-detorsion+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-α) 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-α 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 N-acetyl cysteine treatment can be effective in preventing tissue damage and oxidative stress, which is induced by ischemia-reperfusion 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.

Keywords:

schemia-reperfusion, ovary, N-acetylcysteine, resveratrol,

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