Gut Liver.  2016 Jan;10(1):101-108. 10.5009/gnl14459.

Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor beta Secretion

Affiliations
  • 1Department of Chemistry, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
  • 2Department of Morphology, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico. jventur@correo.uaa.mx
  • 3Department of Pathology, Centenary Hospital Miguel Hidalgo, Aguascalientes, Mexico.
  • 4Department of Physiology, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.

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.

Keyword

Cirrhosis; Adrenergic pathway; Adrenergic receptor antagonist; Collagen; Transforming growth factor beta

MeSH Terms

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
Adrenergic alpha-1 Receptor Antagonists
Alanine Transaminase
Aspartate Aminotransferases
Bilirubin
Carbazoles
Carbon Tetrachloride
Collagen Type I
Doxazosin
Propanolamines
Serum Albumin
Transforming Growth Factor beta
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