Betaine treatment decreased oxidative stress, inflammation, and stellate cell activation in rats with alcoholic liver fibrosis.
The aim of this study was to investigate the effect of betaine (BET) on alcoholic liver fibrosis in rats. Fibrosis was experimentally generated with ethanol plus carbon tetrachloride (ETH+CCl4) treatment. Rats were treated with ETH (5% v/v in drinking water) for 14 weeks. CCl4 was administered intraperitoneally (i.p.) 0.2mL/kg twice a week to rats in the last 6 weeks with/without commercial food containing BET (2% w/w). Serum hepatic damage markers, tumor necrosis factor-α, hepatic triglyceride (TG) and hydroxyproline (HYP) levels, and oxidative stress parameters were measured together with histopathologic observations. In addition, α-smooth muscle-actin (α-SMA), transforming growth factor-β1 (TGF-β1) and type I collagen (COL1A1) protein expressions were assayed immunohistochemically to evaluate stellate cell (HSC) activation. mRNA expressions of matrix metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were also determined. BET treatment diminished TG and HYP levels; prooxidant status and fibrotic changes; α-SMA, COL1A1 and TGF-β protein expressions; MMP-2, TIMP-1 and TIMP-2 mRNA expressions in the liver of fibrotic rats. In conclusion, these results indicate that the antifibrotic effect of BET may be related to its suppressive effects on oxidant and inflammatory processes together with HSC activation in alcoholic liver fibrosis.
Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Çapa, Istanbul, Turkey.
İlknur
İ
Bingül
Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Çapa, Istanbul, Turkey.
Canan
C
Başaran-Küçükgergin
Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Çapa, Istanbul, Turkey.
A Fatih
AF
Aydın
Department of Biochemistry, Yeditepe University Medical Faculty, Kayışdağı, Istanbul, Turkey.
Jale
J
Çoban
Department of Pathology, Yeditepe University Medical Faculty, Kayışdağı, Istanbul, Turkey.
Işın
I
Doğan-Ekici
Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Çapa, Istanbul, Turkey. Electronic address: sdabbasoglu@yahoo.com.
Semra
S
Doğru-Abbasoğlu
Department of Biochemistry, Istanbul Medical Faculty, Istanbul University, Çapa, Istanbul, Turkey.
Müjdat
M
Uysal
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001622:Betaine / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D005260:Female; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008106:Liver Cirrhosis, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D015415:Biomarkers; D001622:Betaine
Alcoholic liver fibrosis; Betaine; Oxidative stress; Rat; Stellate cell activation