title: Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor β Secretion.
abstract: OBJECTIVE
  The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model.
  
  
  METHODS
  Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor β (TGF-β) immunohistochemistry was analyzed.
  
  
  RESULTS
  Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-β-secreting cells.
  
  
  CONCLUSIONS
  Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-β via the blockage of α1- and β-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.
authors.affiliation: Department of Chemistry, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: Martin Humberto
authors.initials: MH
authors.lastname: Muñoz-Ortega
authors.affiliation: Department of Morphology, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: Raúl Wiliberto
authors.initials: RW
authors.lastname: Llamas-Ramírez
authors.affiliation: Department of Morphology, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: Norma Isabel
authors.initials: NI
authors.lastname: Romero-Delgadillo
authors.affiliation: Department of Morphology, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: Tania Guadalupe
authors.initials: TG
authors.lastname: Elías-Flores
authors.affiliation: Department of Morphology, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: Edgar de Jesus
authors.initials: Ede J
authors.lastname: Tavares-Rodríguez
authors.affiliation: Department of Morphology, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: María Del Rosario
authors.initials: Mdel R
authors.lastname: Campos-Esparza
authors.affiliation: Department of Chemistry, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cervantes-García
authors.affiliation: Department of Pathology, Centenary Hospital Miguel Hidalgo, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Muñoz-Fernández
authors.affiliation: Department of Physiology, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: Martin
authors.initials: M
authors.lastname: Gerardo-Rodríguez
authors.affiliation: Department of Morphology, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Ventura-Juárez
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002227:Carbazoles / Q000494:pharmacology*; D002251:Carbon Tetrachloride; D000077261:Carvedilol; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D017292:Doxazosin / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008111:Liver Function Tests; D011412:Propanolamines / Q000494:pharmacology*; D012709:Serum Albumin / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000097:blood / Q000187:drug effects*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D002227:Carbazoles; D024042:Collagen Type I; D011412:Propanolamines; D012709:Serum Albumin; D016212:Transforming Growth Factor beta; D000077261:Carvedilol; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D017292:Doxazosin; D001663:Bilirubin
keywords: Adrenergic pathway; Adrenergic receptor antagonist; Cirrhosis; Collagen; Transforming growth factor beta