α-Lipoik asit ve N-asetilsisteinin sıçan karaciğerinde dietilnitrozamin ve yüksek yağlı diyetin neden olduğu oksidatif stres ve preneoplastik lezyonlar üzerine etkisi

Öz

Amaç: Oksidatif stres ve inflamasyon steatohepatit (NASH), siroz ve hepatoselüler karsinom (HCC) gelişimi için önemlidir. Yüksek yağlı diyet (HFD) promotör görevi görür ve dietilnitrosamin (DEN) ile başlatılan karsinogenez modelinde kanser oluşumunu indükler. DEN + HFD uygulaması diyet, siroz ve kanser arasındaki ilişkiyi araştırmak için uygun bir deneysel model olabilir. Yöntemler: Sıçanlara 4 hafta boyunca DEN (haftada bir kez 50 mg / kg / i.p.) enjekte edildi. 15 gün sonra, sıçanlara HFD tek başına veya α -lipoik asit (ALA; 2 g / kg yem), N-asetilsistein (NAC; içme suyunda % 1 w/v) takviyeleri 12 hafta süreyle verildi. Bulgular: DEN + HFD uygulaması serum hepatik hasar belirteçleri ve hepatik oksidatif stres parametrelerinin (lipit/protein oksidasyon ürünleri) armasına ve fibrotik değişikliklere neden oldu. Ancak, HCC nodülü tespit edilmedi. Hepatik GST-pi ve Ki-67 ekspresyonları de artmış olarak bulunduğundan dolayı, DEN + HFD uygulaması, prekanseröz lezyonlara ve karaciğerde yüksek proliferasyon oranlarına neden oldu. NAC takviyesi, DEN + HFD ile muamele edilen sıçanların karaciğerinde oksidatif stresi ve fibrotik ve preneoplastik lezyonların oluşumunu azalttı. Bununla birlikte, ALA takviyesinin bu lezyonlar üzerinde iyileştirici bir etkisi olmamıştır. ALA ve NAC'nin birlikte uygulanmasıyla hiçbir sinerjistik etki görülmedi. Sonuçlar: Sonuçlarımıza göre, bir antioksidan olan NAC, karaciğerde DEN + HFD'nin neden olduğu artmış oksidatif stresi azaltmada ve preneoplastik lezyonların oluşumu üzerine iyileştirici etkiye sahiptir.

Anahtar Kelimeler

• yüksek yağlı diyet
• dietilnitrozamin
• oksidatif stres
• α-lipoik asid
• N-asetilsistein
• karaciğer hasarı

Effect of α-lipoic acid and N-acetylcysteine on liver oxidative stress, preneoplastic lesions induced by diethylnitrosamine plus high-fat diet

Abstract

Aim: Oxidative stress and inflammation are important for development of nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). High fat diet (HFD) acts as promoter and induces cancer formation by diethylnitrosamine (DEN)-initiated carcinogenesis. DEN+HFD experimental model may be suitable to investigate the relationship between diet, cirrhosis and cancer. Methods: Rats were injected with DEN (50 mg/kg/once a week; i.p.) for 4 weeks. After 15 days, rats received HFD with/without supplementations of α-lipoic acid (ALA; 2 g/kg chow), N-acetylcysteine (NAC; 1% w/v drinking water) and their combination for 12 weeks. Results: DEN+HFD-treatment resulted in increase of serum hepatic damage markers, hepatic oxidative stress parameters (lipid/protein oxidation products) and fibrotic changes. However, no HCC nodule was detected. Hepatic GST-pi and Ki-67 expressions also increased. Accordingly, DEN+HFD-treatment resulted in precancerous lesions and high rate of proliferation in the liver. NAC supplementation decreased hepatic oxidative stress and formation of fibrotic and preneoplastic lesions of DEN+HFD-treated rats. However, ALA supplementation did not have a curative effect on these lesions. No synergistic effect was seen with co-administration of ALA and NAC. Conclusions: According to present results NAC, acting as an antioxidant, has ameliorating effect on DEN+HFD-induced oxidative stress and the formation of preneoplastic lesions in liver.

Keywords

• High fat diet
• diethylnitrosamine
• oxidative stress
• α-lipoic acid
• N-acetylcysteine
• liver injury

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