High-fat diet plus carbon tetrachloride-induced liver fibrosis is alleviated by betaine treatment in rats

Steatosis, the first lesion in non-alcoholic fatty liver disease (NAFLD), may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Steatosis predisposes the liver to oxidative stress, inflammation, and cytokines. Betaine (BET) has antioxidant, antiinflammatory and hepatoprotective effects....

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Published in:International immunopharmacology 2016-10, Vol.39, p.199-207
Main Authors: Bingül, İlknur, Aydın, A. Fatih, Başaran-Küçükgergin, Canan, Doğan-Ekici, Işın, Çoban, Jale, Doğru-Abbasoğlu, Semra, Uysal, Müjdat
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Anti-Inflammatory Agents - therapeutic use
Antioxidants - therapeutic use
Betaine
Betaine - therapeutic use
Carbon Tetrachloride - toxicity
Collagen Type I - metabolism
Diet, High-Fat
Female
Lipid Metabolism - drug effects
Liver - drug effects
Liver - metabolism
Liver - pathology
Liver Cirrhosis - chemically induced
Liver Cirrhosis - drug therapy
Matrix Metalloproteinase 2 - genetics
Matrix Metalloproteinase 2 - metabolism
Non-alcoholic fibrosis
Oxidative stress
Rat
Rats
Rats, Sprague-Dawley
Stellate cell activation
Transforming Growth Factor beta1 - metabolism
Tumor Necrosis Factor-alpha - metabolism
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Summary:Steatosis, the first lesion in non-alcoholic fatty liver disease (NAFLD), may progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Steatosis predisposes the liver to oxidative stress, inflammation, and cytokines. Betaine (BET) has antioxidant, antiinflammatory and hepatoprotective effects. However, the effects of BET on liver fibrosis development are unknown. Rats were treated with high-fat diet (60% of total calories from fat) for 14weeks. Carbon tetrachloride (0.2mL/kg; two times per week; i.p.) was administered to rats in the last 6weeks with/without commercial food containing BET (2%; w/w). Serum liver function tests and tumor necrosis factor-α, insulin resistance, hepatic triglyceride (TG) and hydroxyproline (HYP) levels and oxidative stress parameters were determined along with histopathologic observations. Alpha-smooth muscle-actin (α-SMA), transforming growth factor-β1 (TGF-β1) and type I collagen (COL1A1) protein expressions and mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were evaluated. BET decreased TG and HYP levels, prooxidant status and fibrotic changes in the liver. α-SMA, COL1A1 and TGF-β1 protein expressions, MMP-2, TIMP-1, and TIMP-2 mRNA expressions diminished due to BET treatment. BET has an antifibrotic effect and this effect may be related to its antioxidant and antiinflammatory actions together with suppression on HSC activation. •Fibrosis was induced by high fat diet and carbon tetrachloride treatments in rats.•Effect of betaine (BET) on fibrosis was investigated.•BET showed antifibrotic effects.•BET suppressed oxidative stress, inflammation and hepatic stellate cell activation.
ISSN:1567-5769
1878-1705
DOI:10.1016/j.intimp.2016.07.028