NON-ALKOLİK STEATOHEPATİT OLUŞTURULAN KOBAYLARDA S-ADENOZİLMETIYONİNİN KARACİĞER VE METABOLİK BOZUKLUKLAR ÜZERİNE ETKİSİ

Year 2025, Volume: 88 Issue: 1, 60 - 71, 31.01.2025

İlknur Bingül , Canan Küçükgergin , Abdurrahman Fatih Aydın , Aydın Çevik , Merva Soluk Tekkeşin , Vakur Olgaç , Semra Doğru Abbasoğlu , Müjdat Uysal

https://doi.org/10.26650/IUITFD.1498606

Abstract

Amaç: S-adenozilmetiyonin (SAM), antioksidan ve anti-enflamatuar etkilere ve hepatoprotektif potansiyele sahiptir. Bu çalışmada, yüksek yağ/kolesterollü diyet (YYKD) ile indüklenen non-alkolik steatohepatit (NASH) üzerinde SAM'ın terapötik etkinliği araştırılmıştır.
Gereç ve Yöntem: Bu çalışmada, NASH oluşturmak için kobaylara 10 hafta boyunca YYKD verildi. Hayvanlara, 10 haftalık YYKD uygulamasının son dört haftasında SAM (50 mg/kg, i.p) uygulandı. Serumda hepatik hasar belirteçleri, lipitler (total kolesterol ve trigliserit), inflamatuar sitokin (tümör nekroz faktörü-α ve interlökin-6) düzeyleri ve insülin direnci (HOMA-IR) ölçüldü. Ayrıca, karaciğerde hepatik lipitler, SAM ve sitokrom p450-2E1 (CYP2E1) düzeyleri, prooksidan parametreler (reaktif oksijen türleri, lipid peroksidleri ve protein karbonil) ve antioksidan parametreler (glutatyon düzeyleri ve antioksidan aktivite) ile birlikte fibrotik parametreler (α-düz kas aktin ve transforme edici büyüme faktör-β1 protein ekspresyonları ve hidroksiprolin düzeyleri) belirlendi. Steatozis, inflamasyon ve fibrozis skorları da histopatolojik olarak tespit edildi.
Bulgular: SAM tedavisi, YYKD ile indüklenen NASH'lı kobayların serumunda hepatik hasar belirteçleri, enflamatuar sitokinler düzeyleri ve HOMA-IR düzeylerinde azalmaya neden oldu. Ayrıca, trigliserit ve CYP2E1 düzeyleri ile fibroz belirteçlerindeki yüksek seviyelerin de SAM tedavisine bağlı olarak azaldığı tespit edildi. Bu tedavi, YYKD diyeti ile beslenen kobayların karaciğerinde SAM düzeylerindeki azalmayı, prooksidan ve antioksidan dengesindeki bozukluğu iyileştirdi, steatozis, inflamasyon ve fibrozis skorlarındaki artışları azalttı.
Sonuç: Bu sonuçlar, SAM'ın lipojenez, oksidatif stres, enflamasyon ve fibrozisi azaltarak YYKD ile indüklenen NASH'ta terapotik bir ajan olarak etkili olabileceğini göstermektedir.

Keywords

S-adenozilmetyonin, non-alkolik steatohepatit, yüksek yağlı/kolesterollü diyet, oksidatif stres, inflamatuvar sitokinler, kobay

Project Number

30446

EFFECT OF S-ADENOSYLMETHIONINE ON HEPATIC AND METABOLIC DISORDERS IN GUINEA PIGS WITH NONALCOHOLIC STEATOHEPATITIS

Abstract

Objective: S-adenosylmethionine (SAM) has antioxidant and anti-inflammatory actions and hepatoprotective potential. In this study, the therapeutic effectiveness of SAM was investigated in high-fat/cholesterol diet (HFCD)-induced non-alcoholic steatohepatitis (NASH).
Material and Methods: In this study, guinea pigs were fed a HFCD for ten weeks to induce NASH. SAM (50 mg/kg, i.p.) was administered to the animals during the last four weeks of the 10-week HFCD regimen. Hepatic damage markers, lipid levels (total cholesterol and triglyceride), inflammatory cytokines (tu mour necrosis-α and interleukin-6) levels, and insulin resistance (HOMA-IR) were determined in the serum. Moreover, hepatic lip ids, SAM and cytochrome p450-2E1 (CYP2E1) levels, prooxidant parameters (reactive oxygen species, lipid peroxides and protein carbonyls) and antioxidant parameters (glutathione levels and antioxidant activity) together with fibrosis indicators (α-smooth muscle actin and transforming growth factor-β1 protein expres sions and hydroxyproline levels) were investigated in the liver. Steatosis, inflammation, and fibrosis scores were also detected histopathologically.
Result: SAM treatment diminished the increase in hepatic damage markers, inflammatory cytokine levels, and HOMA-IR levels in the serum of guinea pigs with HFCD-induced NASH. Elevated levels of hepatic triglyceride and CYP2E1 and fibrosis indicators were also detected to decrease due to SAM treatment. This treatment reduced the decrease in SAM levels, disturbance in the prooxidant and antioxidant balance, and diminished the increases in steatosis, inflammation, and fibrosis scores in the liver of guinea pigs fed the HFCD diet.
Conclusion: These results indicate that SAM may be effective in HFCD-induced NASH as a therapeutic agent by decreasing lipogenesis, oxidative stress, inflammation, and fibrosis.

Keywords

S-adenosylmethionine, nonalcoholic steatohepatitis, high fat/cholesterol diet, oxidative stress, inflammatory cytokines, guinea pigs

Ethical Statement

This study was approved by the Animal Care and Use Committee of Istanbul University (Approval no: 02.03.2108-2018/18).

Supporting Institution

The present work was supported by Research Fund of Istanbul University (Project No: 30446).

Project Number

30446

Thanks

We gratefully thank Mr. E. Paul Larkin from Atrium Innovation Inc. (USA) for supporting us in providing S-adenosylmethionine material.

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