title: High-fat diet plus carbon tetrachloride-induced liver fibrosis is alleviated by betaine treatment in rats.
abstract: 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.
authors: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors: İlknur
authors: İ
authors: Bingül
authors: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors: A Fatih
authors: AF
authors: Aydın
authors: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors: Canan
authors: C
authors: Başaran-Küçükgergin
authors: Department of Pathology, Yeditepe University Medical Faculty, Kayışdağı, Istanbul, Turkey.
authors: Işın
authors: I
authors: Doğan-Ekici
authors: Department of Biochemistry, Yeditepe University Medical Faculty, Kayışdağı, Istanbul, Turkey.
authors: Jale
authors: J
authors: Çoban
authors: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey. Electronic address: sdabbasoglu@yahoo.com.
authors: Semra
authors: S
authors: Doğru-Abbasoğlu
authors: Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
authors: Müjdat
authors: M
authors: Uysal
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D001622:Betaine / Q000627:therapeutic use*; D002251:Carbon Tetrachloride / Q000633:toxicity; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D059305:Diet, High-Fat; D005260:Female; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000199:Actins; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001622:Betaine; D002251:Carbon Tetrachloride; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D020778:Matrix Metalloproteinase 2; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C498862:Acta2 protein, rat
keywords: Betaine; Non-alcoholic fibrosis; Oxidative stress; Rat; Stellate cell activation