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Published on: February 10, 2015
Ivermectin Attenuates CCl4-Induced Liver Fibrosis in Mice by Suppressing Hepatic Stellate Cell Activation
Hanglu Ying1, Long Li1,2, Yufen Zhao1,2
1Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China.
Abstract:
Liver fibrosis, a common liver dysfunction with high morbidity and mortality rates, is the leading cause of cirrhosis and hepatocellular carcinoma, for which there are no effective therapies. Ivermectin is an antiparasitic drug that also has been showing therapeutic actions in many other diseases, including antiviral and anticancer actions, as well as treating metabolic diseases. Herein, we evaluated the function of ivermectin in regulating liver fibrosis. Firstly, carbon tetrachloride (CCl4)-injected Balb/c mice were used to assess the antifibrosis effects of ivermectin in vivo. Further, CFSC, a rat hepatic stellate cell (HSC) line, was used to explore the function of ivermectin in HSC activation in vitro. The in vivo data showed that ivermectin administration alleviated histopathological changes, improved liver function, reduced collagen deposition, and downregulated the expression of profibrotic genes. Mechanistically, the ivermectin treatment inhibited intrahepatic macrophage accumulation and suppressed the production of proinflammatory factors. Importantly, the ivermectin administration significantly decreased the protein levels of α-smooth muscle actin (α-SMA) both in vivo and in vitro, suggesting that the antifibrotic effects of ivermectin are mainly due to the promotion of HSC deactivation. The present study demonstrates that ivermectin may be a potential therapeutic agent for the prevention of hepatic fibrosis.
Insights
Ivermectin shows promise in treating liver fibrosis by deactivating hepatic stellate cells (HSCs) and reducing inflammation. This study suggests ivermectin could be a potential therapeutic for preventing liver fibrosis and its complications.
Area of Science:
- Hepatology
- Pharmacology
- Immunology
Background:
- Liver fibrosis is a significant health concern, often leading to cirrhosis and liver cancer, with limited effective treatments.
- Ivermectin, an antiparasitic drug, exhibits diverse therapeutic properties, including antiviral, anticancer, and metabolic regulatory effects.
Purpose of the Study:
- To investigate the potential of ivermectin as a therapeutic agent for liver fibrosis.
- To elucidate the mechanisms by which ivermectin regulates hepatic stellate cell (HSC) activation and liver fibrosis progression.
Main Methods:
- In vivo studies using carbon tetrachloride (CCl4)-induced liver fibrosis in Balb/c mice.
- In vitro studies utilizing a rat hepatic stellate cell (HSC) line (CFSC) to assess ivermectin's effects on HSC activation.
- Histopathological analysis, liver function tests, collagen deposition assessment, gene expression analysis, and protein level determination (α-smooth muscle actin).
Main Results:
- Ivermectin administration in mice alleviated liver damage, improved liver function, reduced collagen deposition, and decreased profibrotic gene expression.
- Ivermectin treatment inhibited intrahepatic macrophage accumulation and suppressed proinflammatory factor production.
- Ivermectin significantly reduced α-smooth muscle actin (α-SMA) levels in both in vivo and in vitro models, indicating promotion of HSC deactivation.
Conclusions:
- Ivermectin demonstrates significant antifibrotic effects in preclinical models.
- The mechanism involves the deactivation of hepatic stellate cells (HSCs) and modulation of inflammatory responses.
- Ivermectin represents a potential therapeutic candidate for the prevention and treatment of liver fibrosis.
