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Pirfenidone effectively reverses experimental liver fibrosis.
García, Leonel; Hernández, Ivan; Sandoval, Ana; Salazar, Adriana; Garcia, Jesus; Vera, Jose; Grijalva, G; Muriel, Pablo; Margolin, Solomon; Armendariz-Borunda, Juan.
Afiliação
  • García L; Institute for Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Apdo. Postal 2-123, Guadalajara, Jal. 44281, Mexico.
J Hepatol ; 37(6): 797-805, 2002 Dec.
Article em En | MEDLINE | ID: mdl-12445421
BACKGROUND/AIMS: Our group has been involved in searching for different strategies to ameliorate hepatic cirrhosis. The aim of this study was to evaluate the effect of Pirfenidone in the reversion or prevention of cirrhosis experimentally induced in rats by chronic administration of CCl(4) and bile-duct ligation (BDL). METHODS: Male cirrhotic Wistar rats (8 weeks of intoxication and then hepatotoxin was discontinued) received either oral saline or Pirfenidone at 500 mg/kg per day. RESULTS: High levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase decreased significantly (P<0.001) in animals treated with Pirfenidone (n=11) with regard to saline-administrated animals (n=9). Prothrombin activity and bilirubins were also reduced. Computerized fibrosis index demonstrated a 70% decrease (P<0.001) along with less hydroxyproline content, reduction in activated HSC and higher active cell regeneration. A rearrangement of the parenchyma was also noted and gene expression of collagens I, III and IV, transforming growth factor beta-1, Smad-7, TIMP-1 and PAI-1 decreased considerably in treated animals. Cirrhotic rats in which CCl(4) was not discontinued displayed 40% liver fibrosis reduction. In a different cirrhosis model, 4-week BDL rats treated with the drug showed a significant 50% reduction in hepatic fibrosis (P<0.01). CONCLUSIONS: This new drug might be useful in healing human disease.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridonas / Cirrose Hepática Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: J Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2002 Tipo de documento: Article País de afiliação: México País de publicação: Holanda
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piridonas / Cirrose Hepática Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: J Hepatol Assunto da revista: GASTROENTEROLOGIA Ano de publicação: 2002 Tipo de documento: Article País de afiliação: México País de publicação: Holanda