OLİVETOL, ANTİOKSİDAN SAVUNMAYI ARTIRARAK OVER İSKEMİ/REPERFÜZYON KAYNAKLI OKSİDATİF VE İNFLAMATUVAR HASARI AZALTIR

Abstract

Over torsiyonu, iskemiye ve bunu takiben gelişen reperfüzyon (İ/R) hasarına yol açarak oksidatif stres, inflamasyon ve doku hasarı oluşturur; bu durum over fonksiyonlarını olumsuz etkileyebilir. Antioksidan ve anti-inflamatuvar özellikleri bilinen doğal bir resorsinol türevi olan Olivetol’ün, over İ/R hasarına karşı koruyucu potansiyeli daha önce değerlendirilmemiştir. Bu deneysel çalışmada, sıçanlar sekiz gruba ayrılmıştır: Sham, Sham + Olivetol (100 mg/kg), İskemi, İskemi + Olivetol (50 mg/kg), İskemi + Olivetol (100 mg/kg), İskemi/Reperfüzyon (İ/R), İ/R + Olivetol (50 mg/kg) ve İ/R + Olivetol (100 mg/kg). İskemi, over pedikülünün 3 saatlik bir süreyle klemplenmesiyle oluşturulmuş, ardından ilgili gruplarda reperfüzyon uygulanmıştır. Olivetol, iskemi veya reperfüzyon indüksiyonu öncesinde oral yoldan verilmiştir. Oksidatif ve inflamatuvar değişiklikleri değerlendirmek amacıyla over dokularında süperoksit dismutaz (SOD), glutatyon (GSH), miyeloperoksidaz (MPO) ve malondialdehit (MDA) düzeyleri analiz edilmiştir. Sham grubuna kıyasla iskemi ve İ/R gruplarında SOD aktivitesi ve GSH düzeyleri anlamlı şekilde azalmış, Olivetol uygulaması ise bu antioksidan parametreleri doza bağlı olarak artırmıştır. Buna karşın, MPO ve MDA düzeyleri iskemi ve reperfüzyon sonrası belirgin şekilde yükselmiş, bu da artmış oksidatif stres ve inflamasyonu göstermiştir; Olivetol tedavisi özellikle 100 mg/kg dozda (p<0.001) bu parametreleri anlamlı düzeyde azaltmıştır. Yüksek doz Olivetol’ün sağlıklı sıçanlarda herhangi bir toksik etkisi gözlenmemiştir. Olivetol, antioksidan savunmayı güçlendirerek ve oksidatif ile inflamatuvar hasarı azaltarak over iskemi/reperfüzyon hasarına karşı anlamlı koruyucu etki göstermiştir. Bu bulgular, Olivetol’ün reperfüzyon kaynaklı over hasarının önlenmesinde ve over fonksiyonlarının korunmasında umut verici bir terapötik aday olabileceğini göstermektedir.

Keywords

• Antioksidan
• İnflamasyon
• Oksidatif stres
• Olivetol
• Over iskemi/reperfüzyonu

Ethical Statement

Bu proje, Atatürk Üniversitesi Veteriner Fakültesi Hayvan Deneyleri Yerel Etik Kurulu tarafından onaylanmıştır (Onay No: 2300251381, Tarih: 17.08.2023).

OLIVETOL MITIGATES OVARIAN ISCHEMIA/REPERFUSION-INDUCED OXIDATIVE AND INFLAMMATORY DAMAGE VIA ENHANCEMENT OF ANTIOXIDANT DEFENSE

Abstract

Ovarian torsion leads to ischemia and subsequent reperfusion (I/R) injury, resulting in oxidative stress, inflammation, and tissue damage that may impair ovarian function. Olivetol, a natural resorcinol derivative with known antioxidant and anti-inflammatory properties, has not been previously evaluated for its protective potential in ovarian I/R injury. In this experimental study, rats were divided into eight groups: Sham, Sham + Olivetol (100 mg/kg), Ischemia, Ischemia + Olivetol (50 mg/kg), Ischemia + Olivetol (100 mg/kg), Ischemia/Reperfusion (I/R), I/R + Olivetol (50 mg/kg), and I/R + Olivetol (100 mg/kg). Ischemia was induced by clamping the ovarian pedicle for 3 hours’ period, followed by reperfusion in relevant groups. Olivetol was administered orally before ischemia or reperfusion induction. Superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO), and malondialdehyde (MDA) levels were analyzed in ovarian tissues to assess oxidative and inflammatory changes. SOD activity and GSH levels were significantly decreased in ischemia and I/R groups compared to the Sham group, whereas Olivetol administration dose-dependently restored these antioxidant parameters. In contrast, MPO and MDA levels were markedly elevated following ischemia and reperfusion, indicating increased oxidative stress and inflammation; these parameters were significantly reduced by Olivetol treatment, particularly at the 100 mg/kg dose (p<0.001). High-dose Olivetol showed no toxic effects in healthy rats. Olivetol exerted significant protective effects against ovarian ischemia/reperfusion injury by enhancing antioxidant defenses and reducing oxidative and inflammatory damage. These findings suggest that Olivetol may represent a promising therapeutic candidate for preventing reperfusion-induced ovarian injury and preserving ovarian function.

Keywords

• Antioxidant
• Inflammation
• Olivetol
• Ovarian ischemia/reperfusion
• Oxidative stress

Ethical Statement

This project was approved by the Local Ethics Committee for Animal Experiments of the Faculty of Veterinary Medicine at Atatürk University (approval number: 2300251381, Date: 17.08.2023).

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