Protective Effects of Folic Acid Against Indomethacin-Induced Liver Injury: Involvement of Nrf2/HO-1, NF-κB, and Apoptotic Signaling Pathways

Öz

The main objective of this study was to evaluate the protective effect of folic acid (FA) against indomethacin (IND)-induced hepatotoxicity in rats. The study assessed the effectiveness of FA in reducing oxidative stress-induced liver damage in rats. The findings showed that FA administration significantly reduced liver damage compared to the control group. Evaluation of the enzymatic antioxidant profile revealed a significant decrease in the activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) enzymes, as well as GSH levels, in the IND-treated group compared to the FA group. FA treatment reduced malondialdehyde (MDA) levels, a key biomarker of lipid peroxidation. FA treatment significantly suppressed pro-inflammatory molecules, particularly by reducing interleukin-1 beta (IL-1β) expression and attenuating nuclear factor kappa-B (NF-κB) activation. Furthermore, FA administration reduced increases in the IND-induced proapoptotic proteins Bax and Caspase-3, while increasing the transcriptional activity of the antiapoptotic gene B-cell lymphoma-2 (Bcl-2). In addition, FA reduced IND-induced liver tissue damage by decreasing alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. Regarding markers used to determine the degree of oxidative stress, a decrease in Nrf-2 and HO-1 levels and an increase in Keap1 levels were observed in the IND group. In the IND+FA group, a statistically significant increase in Nrf-2 and HO-1 levels and a decrease in Keap1 were observed compared to the IND group. The study results indicate that FA administration can alleviate liver tissue damage caused by IND toxicity.

Anahtar Kelimeler

• Apoptosis
• Folic acid
• Hepatotoxicity
• Indomethacin
• Liver.

Destekleyen Kurum

None

Teşekkür

None

Folik Asidin İndometasin Kaynaklı Karaciğer Hasarına Karşı Koruyucu Etkileri: Nrf2/HO-1, NF-κB ve Apoptotik Sinyal Yollarının Rolü

Öz

Bu çalışmanın temel amacı, sıçanlarda indometasin (IND) kaynaklı hepatotoksisiteye karşı folik asidin (FA) koruyucu etkisini değerlendirmektir. Çalışmada, sıçanlarda oksidatif stres kaynaklı karaciğer hasarını azaltmada FA'nın etkinliği değerlendirildi. Bulgular, FA uygulamasının kontrol grubuna kıyasla karaciğer hasarını önemli ölçüde azalttığını gösterdi. Enzimatik antioksidan profilinin değerlendirilmesi, IND uygulanan grupta katalaz (CAT), glutatyon peroksidaz (GPx) ve süperoksit dismutaz (SOD) enzimlerinin aktivitelerinde ve GSH seviyelerinde FA grubuna kıyasla önemli bir azalma olduğunu ortaya koydu. FA tedavisi, lipid peroksidasyonunun önemli bir biyobelirteci olan malondialdehit (MDA) seviyelerini düşürdü. FA tedavisi, özellikle interlökin-1 beta (IL-1β) ekspresyonunu azaltarak ve nükleer faktör kappa-B (NF-κB) aktivasyonunu hafifleterek proinflamatuar molekülleri önemli ölçüde baskıladı. Ayrıca, FA uygulaması, IND kaynaklı proapoptotik proteinler Bax ve Caspase-3'teki artışları azaltırken, antiapoptotik gen B-hücreli lenfoma-2'nin (Bcl-2) transkripsiyonel aktivitesini artırdı. Bunun yanında FA, alanin aminotransferaz (ALT) ve alkalin fosfataz (ALP) seviyelerini düşürerek IND kaynaklı karaciğer dokusu hasarını azalttı. Oksidatif stresin derecesini belirlemek için kulanılan belirteçlerden, IND grubunda Nrf-2 ve HO-1 seviyelerinde azalma ve Keap1 seviyelerinde artış gözlemlendi. IND+FA grubunda ise, IND grubuna kıyasla Nrf-2 ve HO-1 seviyelerinde istatistiksel olarak anlamlı bir artış ve Keap1'de azalma gözlemlendi. Çalışma sonuçları, FA uygulamasının IND toksisitesinin neden olduğu karaciğer dokusu hasarını hafifletebileceğini gösterdi.

Anahtar Kelimeler

• Apoptozis
• Folik Asit
• Hepatotoksisite
• İndometazin
• Karaciğer.

Destekleyen Kurum

Yok.

Teşekkür

Yok.

Kaynakça

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