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

• Published in: International immunopharmacology Vol. 39; pp. 199 - 207
• Main Authors: Bingül, İlknur, Aydın, A. Fatih, Başaran-Küçükgergin, Canan, Doğan-Ekici, Işın, Çoban, Jale, Doğru-Abbasoğlu, Semra, Uysal, Müjdat
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2016
• 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; Oxidative stress; H and E; NAFLD; Rat; HFD; ALT; MDA; Stellate cell activation; LDH; α-SMA; Betaine; HSC; FRAP; CHOL; GSH; HYP; AST; GSH-Px; GST; HCC; IR; SOD; NASH; ECM; BET; COL1A1; TIMP-1 and TIMP-2; PC; TG; MMP-2; TNF-α; CAT; CCl4; ROS; TGF-β1; HOMA; MTC; Non-alcoholic fibrosis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2016.07.028

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.