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Published on: February 10, 2015
The α-1 Adrenergic Receptor Antagonist Doxazosin Attenuates Liver Fibrosis by Alleviating Sinusoidal Capillarization
Ai-Yuan Xiu1, Qian Ding2, Chang-Peng Zhu3
1Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China.
Abstract:
Liver fibrosis and cirrhosis, which are caused by chronic liver injury, represent common and intractable clinical challenges of global importance. However, effective therapeutics are lacking. Therefore, the study examines the effect of doxazosin on liver fibrosis. Carbon tetrachloride (CCl4) is injected into mice to establish a liver fibrosis model. Doxazosin (5 and 10 mg/kg) is administered daily by gavage. HE staining, Masson staining, Sirius Red staining, scanning electron microscopy, western blotting, real-time PCR, and immunofluorescence analysis are performed to estimate liver fibrosis and sinusoidal capillarization in mice. Cell Counting Kit-8 assays, western blotting, immunofluorescence analysis, tube formation, and transwell migration assays are performed on human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs) to elucidate the potential mechanism of doxazosin. Doxazosin alleviates liver fibrosis and sinusoidal capillarization in CCl4-induced mice. Angiogenesis is attenuated by doxazosin in HUVECs and HHSECs. This study demonstrates that doxazosin attenuated liver fibrosis by alleviating sinusoidal capillarization and liver angiogenesis.
Insights
Doxazosin effectively reduces liver fibrosis and sinusoidal capillarization in a mouse model. This study suggests doxazosin as a potential therapeutic for liver diseases by inhibiting liver angiogenesis.
Area of Science:
- Hepatology
- Pharmacology
- Cell Biology
Background:
- Liver fibrosis and cirrhosis are critical global health issues stemming from chronic liver injury.
- Current therapeutic options for these conditions remain limited, necessitating novel treatment strategies.
Purpose of the Study:
- To investigate the therapeutic potential of doxazosin in mitigating liver fibrosis.
- To elucidate the underlying mechanisms by which doxazosin affects liver fibrosis and angiogenesis.
Main Methods:
- A mouse model of liver fibrosis was induced using carbon tetrachloride (CCl4) administration.
- Doxazosin was administered orally to mice, and liver fibrosis was assessed using histological staining (HE, Masson, Sirius Red) and molecular techniques.
- In vitro studies on human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs) involved cell viability, western blotting, immunofluorescence, and angiogenesis assays.
Main Results:
- Doxazosin treatment significantly alleviated liver fibrosis and sinusoidal capillarization in CCl4-induced mice.
- The drug demonstrated an inhibitory effect on angiogenesis in both HUVECs and HHSECs.
- Doxazosin reduced liver angiogenesis and sinusoidal capillarization.
Conclusions:
- Doxazosin shows promise in treating liver fibrosis by targeting sinusoidal capillarization and angiogenesis.
- The findings support doxazosin as a potential therapeutic agent for chronic liver injury.
- Further research into doxazosin's role in liver disease is warranted.
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