Genistein modifies liver fibrosis and improves liver function by inducing uPA expression and proteolytic activity in CCl4-treated rats.
OBJECTIVE
To evaluate the effect of genistein on the fibrosis and matrix degradation caused by experimentally induced fibrosis in rats.


METHODS
Hepatic fibrosis was brought about by chronic administration of carbon tetrachloride to rats. To evaluate the effect of genistein on liver fibrosis and function, total collagen content and proteolytic activity in the liver were quantified. Urokinase-type plasminogen activator (uPA) expression during experimental fibrosis was localized by immunohistochemistry. Histopathological changes were evaluated using light and electron microscopy.


RESULTS
Animals with fibrosis and treated with genistein showed an important reduction (73%) in hepatic collagen content as well as an improvement in liver function (p < 0.001). Genistein increased the capacity of the liver to degrade type I collagen and Matrigel (3.1- and 3.7-fold, respectively; p < 0.001) in animals with liver fibrosis. Genistein increased the number of uPA-immunoreactive cells. The increase in the uPA expression correlated with an increase in proteolytic activity. Histological analysis revealed a reduction in the number of fiber septa in pericentral and perisinusoidal areas. Transmission electron micrographs of livers from animals with fibrosis and treated with genistein showed a reduction in the number of hepatic stellate cells activated and a smaller number of collagen fibers.


CONCLUSIONS
Genistein is able to improve the liver after injury and fibrosis induced by chronic administration of carbon tetrachloride. This finding suggests that genistein has antifibrogenic potential and could therefore be useful for treating chronic liver disease.
Salas
Alfonso Leija
AL
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México.
Montezuma
Tania Díaz
TD
Fariña
German Garrido
GG
Reyes-Esparza
Jorge
J
Rodríguez-Fragoso
Lourdes
L
D000818:Animals; D002251:Carbon Tetrachloride; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D008103:Liver Cirrhosis / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D046529:Microscopy, Electron, Transmission; D010447:Peptide Hydrolases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*