Abstract
Liver fibrosis is an important process that occurs in most types of chronic liver diseases and often results in the end stage of liver diseases, such as cirrhosis, portal hypertension, and hepatocellular carcinoma. Sorafenib, a multiple tyrosine kinase inhibitor, has been shown to inhibit liver fibrosis in multiple experimental fibrosis mouse and rat models. The aim of this study was to test the therapeutic effect of sorafenib on liver fibrosis induced by infection with a parasite, Schistosoma japonicum, in mice. Mice were percutaneously infected through the abdomen with Schistosoma cercariae to develop a schistosomula liver fibrosis model. Eight weeks after infection, infected mice were treated with the anti-parasitic agent praziquantel for 2 days and sorafenib for 2 weeks. Hepatic histopathological changes were assessed using hematoxylin and eosin (HE) and Masson’s trichome staining. The hepatic expression levels of collagen I, collagen III, alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and PDGF receptor-beta (PDGFR-β) were analyzed by immunohistochemistry and western blot. Praziquantel administration alone but not sorafenib reduced liver fibrosis, and the combination of praziquantel and sorafenib significantly attenuated liver fibrosis in S. japonicum-infected mice. Moreover, sorafenib plus praziquantel markedly decreased the hepatic deposition of collagen and expression of fibrogenic genes in these mice. In conclusion, the use of sorafenib following praziquantel treatment may represent a potential therapeutic strategy for liver fibrosis induced by S. japonicum in patients.
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Abbreviations
- S. japonicum :
-
Schistosoma japonicum
- HE:
-
hematoxylin and eosin
- α-SMA:
-
alpha-smooth muscle actin
- PDGF:
-
platelet-derived growth factor
- PDGFR-β:
-
PDGF receptor-beta
- HCC:
-
hepatocellular carcinoma
- ECM:
-
extracellular matrix
- HSCs:
-
hepatic stellate cells
- TGF-β:
-
transforming growth factor beta
- PZQ:
-
praziquantel
- ALT:
-
alanine aminotransferase
- ALB:
-
albumin
- Schistosoma mansoni :
-
S. mansoni
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Acknowledgements
We thank Dr. Yuanyuan Cao from State Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University for excellent technical assistance.
Funding
This work was supported by grants from the National Science Foundation, China (81401663) and grants from Health and Family Planning Commission of HuBei Province, China (XF2012-22).
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Conceived and designed the experiments: YX, ZYM, and XL. Performed the experiments: ZYM, XL, HFD, and LXW. Analyzed the data: ZYM, YX, XL, HFD, YC, and DX. Contributed reagents/materials/analysis tools: ZYM, YX, XL, HFD, and DX. Wrote the paper: ZYM, XL, YC, and YX. All authors read and approved the final manuscript.
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All animals were maintained according to the guidelines of the animal facility at the Hubei Provincial Academy of Preventive Medicine. All animal experiments were conducted in accordance with the Guide for the Care and Use of Laboratory and approved by the Committee on the Ethics of Animal Experiments of Hubei Provincial Academy of Preventive Medicine (project number M2014001).
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Section Editor: Christoph G. Grevelding
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Ma, Z., Liu, X., Dong, H. et al. Sorafenib and praziquantel synergistically attenuate Schistosoma japonicum-induced liver fibrosis in mice. Parasitol Res 117, 2831–2839 (2018). https://doi.org/10.1007/s00436-018-5972-x
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DOI: https://doi.org/10.1007/s00436-018-5972-x