Coffee attenuates fibrosis by decreasing the expression of TGF-β and CTGF in a murine model of liver damage.
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.
Departamento de Farmacología, Cinvestav-IPN, Apdo Postal 14-740, México, 07000, D. F., México.
Jonathan
J
Arauz
Marina Galicia-
MG
Moreno
Pedro
P
Cortés-Reynosa
Eduardo Pérez
EP
Salazar
Pablo
P
Muriel
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003069:Coffee / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005355:Fibrosis; D005979:Glutathione Peroxidase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000178:diet therapy* / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000633:toxicity; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000097:blood
D000199:Actins; D000975:Antioxidants; D003069:Coffee; D016212:Transforming Growth Factor beta; D013853:Thioacetamide; D055513:Connective Tissue Growth Factor; D003094:Collagen; D005979:Glutathione Peroxidase; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat