Coffee attenuates fibrosis by decreasing the expression of TGF-β and CTGF in a murine model of liver damage

J Appl Toxicol. 2013 Sep;33(9):970-9. doi: 10.1002/jat.2788. Epub 2012 Aug 17.

Abstract

This study was performed to evaluate the antifibrotic properties of coffee in a model of liver damage induced by repeated administration of thioacetamide (TAA) in male Wistar rats. In this study, cirrhosis was induced by chronic TAA administration and the effects of co-administration of conventional caffeinated coffee or decaffeinated coffee (CC, DC, respectively) for 8 weeks were evaluated. TAA administration elevated serum alkaline phosphatase (AP), γ-glutamyl transpeptidase (γ-GTP) and alanine aminotransferase (ALAT), liver lipid peroxidation, collagen content, depleted liver glycogen and glutathione peroxidase (GPx) activity. Additionally increased levels of a number of proteins were detected including transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF) and alpha-smooth muscle actin (α-SMA), and matrix metalloproteinase (MMP)-2, 9 and 13. Coffee suppressed most of the changes produced by TAA. Histopathological analysis was in agreement with biochemical and molecular findings. These results indicate that coffee attenuates experimental cirrhosis; the action mechanisms are probably associated with its antioxidant properties and mainly by its ability to block the elevation of the profibrogenic cytokine TGF-β and its downstream effector CTGF. Various components of coffee that have been related to such a favorable effect include caffeine, coffee oils kahweol, cafestol and antioxidant substances; however, no definite evidence for the role of these components has been established. These results support earlier findings suggesting a beneficial effect of coffee on the liver. However, more basic clinical studies must be performed to confirm this hypothesis.

Keywords: CTGF; TGF-β; antioxidants; coffee; liver injury; thioacetamide.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Animals
  • Antioxidants / pharmacology
  • Coffee / chemistry*
  • Collagen / metabolism
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism*
  • Disease Models, Animal
  • Fibrosis
  • Glutathione Peroxidase / blood
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / diet therapy*
  • Liver Cirrhosis / pathology
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Rats
  • Rats, Wistar
  • Thioacetamide / toxicity
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • gamma-Glutamyltransferase / blood

Substances

  • Actins
  • Antioxidants
  • Coffee
  • Transforming Growth Factor beta
  • Thioacetamide
  • Connective Tissue Growth Factor
  • Collagen
  • Glutathione Peroxidase
  • gamma-Glutamyltransferase
  • Alanine Transaminase
  • Alkaline Phosphatase
  • Matrix Metalloproteinase 13
  • Mmp13 protein, rat
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat