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Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in
Martin Humberto Muñoz-Ortega1, Raúl Wiliberto Llamas-Ramírez2, Norma Isabel Romero-Delgadillo2
1Department of Chemistry, Center of Basic Sciences, Autonomous University of Aguascalientes, Aguascalientes, Mexico.
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 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.
Insights
Carvedilol and doxazosin improved liver function and reduced fibrosis in a hamster cirrhosis model. These adrenergic receptor antagonists decreased collagen and transforming growth factor-beta (TGF-β), suggesting a potential therapeutic strategy for liver fibrosis.
Area of Science:
- Pharmacology
- Hepatology
- Fibrosis Research
Background:
- Cirrhosis treatment is a key research area.
- Adrenergic receptor antagonists show potential as antifibrotic agents.
- Previous studies evaluated these drugs in rodent models.
Purpose of the Study:
- To assess carvedilol and doxazosin effects on liver fibrosis.
- To use a hamster model for cirrhosis and fibrosis evaluation.
Main Methods:
- Hamsters with induced cirrhosis received daily carvedilol or doxazosin for 6 weeks.
- Hepatic function assessed via biochemical markers (bilirubin, AST, ALT, albumin).
- Liver tissue analyzed histologically for collagen and transforming growth factor-beta (TGF-β).
Main Results:
- Doxazosin and carvedilol treatments restored hepatic function.
- Histological analysis revealed reduced collagen type I deposits.
- A decrease in TGF-β-secreting cells was observed.
Conclusions:
- Carvedilol and doxazosin reduce liver fibrosis by inhibiting TGF-β.
- Blocking α1- and β-adrenergic receptors diminishes profibrotic activity.
- These findings support the antifibrotic potential of these drugs in cirrhosis.
