Investigation of the Effects of Resveratrol on Paracetamol Toxicity Established in Hep3B Cells

Öz

Aim: We therefore wanted to investigate acetaminophen hepatotoxicity by using Hep3B human hepatoma cells exposed to acetaminophen and resveratrol, used as a protective agent. Specifically, we studied the role of some proinflammatory markers and oxidative damage as possible mechanisms of acetaminophen-associated cytotoxicity. Materials and Method: The Hep3B human hepatoma cell line was used for this study. In vitro studies (GSH, SOD, CAT, AST, ALT, TNF-alpha, IL-6 and cell viability) were performed by using different methods such as Biochemical analyzer, RT-PCR, ELISA and MTT. Acetaminophen and resveratrol were applied to cells in a different time and doses. Results: Only acetaminophen treatment decreased SOD, CAT and GSH levels in Hep3B cells whereas acetaminophen and resveratrol co-treatment increased these enzymes levels. On the other hand, acetaminophen and resveratrol co-treatment (especially 160 µM dose of resveratrol) lead a severe increase in TNF-alpha and IL-6 levels. Conclusion: It is shown that acetaminophen has caused hepatotoxicity but interestingly but resveratrol treatment effects the related parameters mentioned above. Only, acetaminophen administration may cause abnormal decreases and/or increases in antioxidant enzymes and proinflammatory cytokines levels. Additionally, acetaminophen and high dose resveratrol co-treatment triggered the inflammation and oxidative stress. These results showed that resveratrol have a potential to be an effective agent on the treatment and protection of hepatic damage.

Anahtar Kelimeler

• Acetaminophen
• Hepatotoxicity
• Hep3B
• Oxidative stress
• Resveratrol
• Cytokines

Resveratrolün Hep3B Hücrelerinde Oluşturulan Parasetamol Toksisitesi Üzerindeki Etkilerinin Araştırılması

Öz

Amaç: Mevcut çalışmada, asetamonifen ve muhtemel koruyucu etkisinin olabileceğini düşündüğümüz resveratrol’ün uygulandığı Hep3B insan hepatoma hücrelerinde oluşturulmuş asetaminofen kaynaklı hepatotoksisitenin incelenmesi amaçlanmıştır. Bu çalışmada özellikle bazı proinflamatuvar parametrelerin rolü ve asetaminofen-aracılı sitotoksisitenin muhtemel sebeplerinden biri olan oksidatif stres araştırılmıştır. Materyal ve Metot: Bu çalışma için Hep3B insan hepatoma hücre hattı kullanılmıştır. İn vitro çalışmalar (GSH, SOD, KAT, AST, ALT, TNF-alfa, IL-6 ve canlılık analiz testi), Biyokimyasal analizatör, ELISA, Real-Time PCR ve MTT gibi farklı metotlar kullanılarak gerçekleştirilmiştir. Asetaminofen ve resveratrol, hücrelere farklı doz ve zamanlarda uygulanmıştır. Bulgular: Hep3B hücrelerinde yalnızca asetaminofen uygulanan gruplarda SOD, KAT ve GSH seviyelerinde azalma tespit edilirken, asetaminofen ve resveratrol’ün beraber uygulandığı gruplarda bu enzimlere ait seviyeleri yükselmiştir. Diğer yandan, asetaminofen ve beraberinde yapılan resveratrol uygulamaları (özellikle 160 µM resveratrol dozu) TNF-alfa ve IL-6 seviyesinde ciddi bir artışa sebep olmuştur. Sonuç: Mevcut çalışmada, asetaminofen’in karaciğer toksisitesine sebep olduğunu ve ilginç bir şekilde resveratrol uygulamaları yukarıda belirtilen parametrelerin seviyelerini ciddi derecede etkilediği gösterilmiştir. Yalnızca asetaminofen uygulaması pro- inflamatuvar sitokin seviyelerinde ve anti-oksidant enzim seviyelerinde anormal artış ve/veya azalışlara sebep olmuştur. Buna ilaveten asetaminofen ile beraber yapılan yüksek doz resveratrol uygulaması inflamasyon ve oksidatif stres oluşumuna öncülük etmiştir. Bu sonuçlar, resveratrol’ün hepatik hasarın önlenmesi ve tedavisinde oldukça etkili bir ajan olabileceğini göstermektedir.

Anahtar Kelimeler

• Asetaminofen
• Hepatotoksisite
• Hep3B
• Oksidatif stres
• Resveratrol
• Sitokinler.

Kaynakça

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