Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor beta Secretion.
- Author:
Martin Humberto MUNOZ-ORTEGA
1
;
Raul Wiliberto LLAMAS-RAMIREZ
;
Norma Isabel ROMERO-DELGADILLO
;
Tania Guadalupe ELIAS-FLORES
;
Edgar DE JESUS TAVARES-RODRIGUEZ
;
Maria DEL ROSARIO CAMPOS-ESPARZA
;
Daniel CERVANTES-GARCIA
;
Luis MUNOZ-FERNANDEZ
;
Martin GERARDO-RODRIGUEZ
;
Javier VENTURA-JUAREZ
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: Cirrhosis; Adrenergic pathway; Adrenergic receptor antagonist; Collagen; Transforming growth factor beta
- MeSH: Adrenergic alpha-1 Receptor Antagonists/*pharmacology; Alanine Transaminase/blood; Animals; Aspartate Aminotransferases/blood; Bilirubin/blood; Carbazoles/*pharmacology; Carbon Tetrachloride; Collagen Type I/drug effects/metabolism; Cricetinae; Doxazosin/*pharmacology; Liver/metabolism/pathology; Liver Cirrhosis/blood/chemically induced/*drug therapy; Liver Function Tests; Propanolamines/*pharmacology; Serum Albumin/analysis; Transforming Growth Factor beta/blood/*drug effects
- From:Gut and Liver 2016;10(1):101-108
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: 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 beta (TGF-beta) 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-beta-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-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.
