Genistein Modifies Liver Fibrosis and Improves Liver Function by Inducing uPA Expression and Proteolytic Activity in CCl<sub>4</sub>-Treated Rats

Vol. 81, No. 1, 2008

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Original Paper

Genistein Modifies Liver Fibrosis and Improves Liver Function by Inducing uPA Expression and Proteolytic Activity in CCl₄-Treated Rats
Alfonso Leija Salas^a, Tania Díaz Montezuma^a, German Garrido Fariña^b, Jorge Reyes-Esparza^a, Lourdes Rodríguez-Fragoso^a

^aFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, y
^bFES-Cuautitlán, Universidad Nacional Autónoma de México, Cuautitlán, Izcalli, México

Address of Corresponding Author

Pharmacology 2008;81:41-49 (DOI: 10.1159/000107968)

Key Words

Genistein
Fibrosis
Extracellular matrix
Collagen
Hepatic stellate cell

Abstract

Aim: 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. Conclusion: 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.

Author Contacts

Lourdes Rodríguez Fragoso, PhD
Flavio García No. 32
Presidentes Ejidales
México D.F. 04470 (México)
Tel./Fax +52 5695 2760, E-Mail mlrodrig1@yahoo.com.mx

Article Information

Received: March 13, 2007
Accepted: May 14, 2007
Published online: September 7, 2007
Number of Print Pages : 9
Number of Figures : 6, Number of Tables : 2, Number of References : 47

Medline Abstract (ID 17823541)

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