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Dergiler / Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi / 2026 / Cilt: 6 Sayı: 2

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

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

Ender Erdoğan(ATATURK UNIVERSITY)0000-0003-4360-6013
Özge Kandemir(AKSARAY ÜNİVERSİTESİ, AKSARAY TEKNİK BİLİMLER MESLEK YÜKSEKOKULU, GIDA İŞLEME BÖLÜMÜ)0000-0001-8884-4168
Sayfa
110–119
Yayın Tarihi
2026-09-23
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Bulgular, FA uygulamasının kontrol grubuna kıyasla karaciğer hasarını önemli ölçüde azalttığını gösterdi.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Bu çalışmanın temel amacı, sıçanlarda indometasin (IND) kaynaklı hepatotoksisiteye karşı folik asidin (FA) koruyucu etkisini değerlendirmektir.
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Temel Bulgular & Veri:Çalışmada, sıçanlarda oksidatif stres kaynaklı karaciğer hasarını azaltmada FA'nın etkinliği değerlendirildi.
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Sonuç & Katkı:Bulgular, FA uygulamasının kontrol grubuna kıyasla karaciğer hasarını önemli ölçüde azalttığını gösterdi.
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Apoptozis · Folik Asit · Hepatotoksisite

Özet

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.

Abstract

The aim of protective role of folic acid (FA) against indomethacin (IND)-induced hepatotoxicity in rats. In particular, the study focused on the capacity of FA to mitigate oxidative stress-related hepatic injury. The results demonstrated that FA treatment markedly attenuated liver damage when compared with the untreated control group. Antioxidant defense system revealed that IND administration led to significant reduction in catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities, together with decreased glutathione (GSH) levels, whereas these parameters were improved following FA treatment. Moreover, FA administration lowered malondialdehyde (MDA) concentrations, an important indicator of lipid peroxidation. FA also exhibited notable anti-inflammatory effects by suppressing proinflammatory mediators, particularly through downregulation of interleukin-1 beta (IL-1β) expression and inhibition of nuclear factor kappa-B (NF- κB) activation. In addition, FA reduced the IND-induced elevation of the proapoptotic proteins Bcl-2-associated X protein (Bax) and cysteine-aspartic protease-3 (Caspase-3), while enhancing the transcriptional activity of the antiapoptotic gene B-cell lymphoma-2 (Bcl-2). Biochemical analyses further indicated that FA alleviated hepatic tissue injury by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels elevated by IND exposure. With respect to oxidative stress-associated signaling pathways, the IND-treated group exhibited decreased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) levels alongside increased Keap1 expression. In contrast, IND+FA group showed a statistically significant increase in Nrf2 and HO-1 levels and a reduction in Keap1 expression relative to the IND group. Overall, these findings suggest that FA exerts a protective effect against IND-induced liver toxicity and may alleviate hepatic damage through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

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Bu Makaleye Atıf Yap

Erdoğan, E., Kandemir, Ö. (2026). Folik Asidin İndometasin Kaynaklı Karaciğer Hasarına Karşı Koruyucu Etkileri: Nrf2/HO-1, NF-κB ve Apoptotik Sinyal Yollarının Rolü. Laboratuvar Hayvanları Bilimi ve Uygulamaları Dergisi, Cilt: 6 Sayı: 2, 110–119. https://doi.org/10.62425/jlasp.1932861

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