New insight into the antifibrotic effects of praziquantel on mice in infection with Schistosoma Japonicum

Yue Jin Liang, Jie Luo, Quan Yuan, Dan Zheng, Ya Ping Liu, Lei Shi, Ying Zhou, Ai Ling Chen, Yong Ya Ren, Ke Yi Sun, Yan Sun, Yong Wang, Zhao Song Zhang

Research output: Contribution to journalArticle

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Abstract

Background: Schistosomiasis is a parasitic disease infecting more than 200 million people in the world. Although chemotherapy targeting on killing schistosomes is one of the main strategies in the disease control, there are few effective ways of dealing with liver fibrosis caused by the parasite infection in the chronic and advanced stages of schistosomiasis. For this reason, new strategies and prospective drugs, which exert antifibrotic effects, are urgently required. Methods and Findings: The antifibrotic effects of praziquantel were assessed in the murine models of schistosomiasis japonica. Murine fibrosis models were established by cutaneous infection with 14±2 Schistosoma japonicum cercariae. Then, the mice of both chronic (8 weeks post-infection) and advanced (15 weeks post-infection) schistosomiasis were treated by gavage of praziquantel (250 mg/kg, once daily for 3 days) to eliminate worms, and followed by praziquantel anti-fibrosis treatment (300 mg/kg, twice daily for 30 days). The fibrosis-related parameters assessed were areas of collagen deposition, content of hydroxyproline and mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9, TIMP1, IL-4, IL-10, IL-13 and IFN-γ of liver. Spleen weight index, alanine aminotransferase activity and liver portal venous pressure were also measured. The results showed that anti-fibrosis treatment improved liver fibrosis, splenomegaly, hepatic function, as well as liver portal hypertension. In order to confirm the anti-fibrotic properties of praziquantel, we established a CCL4-induced model and revealed that CCL4-induced liver fibrosis was inhibited by PZQ treatment for 30 days. Furthermore, we analyzed the effects of praziquantel on mouse primary hepatic stellate cells (HSCs). It is indicated that mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9 and TIMP1 of HSCs were all inhibited after praziquantel anti-parasite treatments. Conclusions: The significant amelioration of hepatic fibrosis by praziquantel treatment validates it as a promising drug of anti-fibrosis and offers potential of a new chemotherapy for hepatic fibrosis resulting from schistosomiasis.

Original languageEnglish (US)
Article numbere20247
JournalPLoS One
Volume6
Issue number5
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

Schistosoma japonicum
praziquantel
Praziquantel
liver cirrhosis
Liver
Fibrosis
fibrosis
schistosomiasis
Schistosomiasis
mice
Infection
infection
liver
Liver Cirrhosis
Hepatic Stellate Cells
Parasitic Diseases
Chemotherapy
drug therapy
Schistosomiasis japonica
portal hypertension

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

New insight into the antifibrotic effects of praziquantel on mice in infection with Schistosoma Japonicum. / Liang, Yue Jin; Luo, Jie; Yuan, Quan; Zheng, Dan; Liu, Ya Ping; Shi, Lei; Zhou, Ying; Chen, Ai Ling; Ren, Yong Ya; Sun, Ke Yi; Sun, Yan; Wang, Yong; Zhang, Zhao Song.

In: PLoS One, Vol. 6, No. 5, e20247, 2011.

Research output: Contribution to journalArticle

Liang, YJ, Luo, J, Yuan, Q, Zheng, D, Liu, YP, Shi, L, Zhou, Y, Chen, AL, Ren, YY, Sun, KY, Sun, Y, Wang, Y & Zhang, ZS 2011, 'New insight into the antifibrotic effects of praziquantel on mice in infection with Schistosoma Japonicum', PLoS One, vol. 6, no. 5, e20247. https://doi.org/10.1371/journal.pone.0020247
Liang, Yue Jin ; Luo, Jie ; Yuan, Quan ; Zheng, Dan ; Liu, Ya Ping ; Shi, Lei ; Zhou, Ying ; Chen, Ai Ling ; Ren, Yong Ya ; Sun, Ke Yi ; Sun, Yan ; Wang, Yong ; Zhang, Zhao Song. / New insight into the antifibrotic effects of praziquantel on mice in infection with Schistosoma Japonicum. In: PLoS One. 2011 ; Vol. 6, No. 5.
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AU - Shi, Lei

AU - Zhou, Ying

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AU - Ren, Yong Ya

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N2 - Background: Schistosomiasis is a parasitic disease infecting more than 200 million people in the world. Although chemotherapy targeting on killing schistosomes is one of the main strategies in the disease control, there are few effective ways of dealing with liver fibrosis caused by the parasite infection in the chronic and advanced stages of schistosomiasis. For this reason, new strategies and prospective drugs, which exert antifibrotic effects, are urgently required. Methods and Findings: The antifibrotic effects of praziquantel were assessed in the murine models of schistosomiasis japonica. Murine fibrosis models were established by cutaneous infection with 14±2 Schistosoma japonicum cercariae. Then, the mice of both chronic (8 weeks post-infection) and advanced (15 weeks post-infection) schistosomiasis were treated by gavage of praziquantel (250 mg/kg, once daily for 3 days) to eliminate worms, and followed by praziquantel anti-fibrosis treatment (300 mg/kg, twice daily for 30 days). The fibrosis-related parameters assessed were areas of collagen deposition, content of hydroxyproline and mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9, TIMP1, IL-4, IL-10, IL-13 and IFN-γ of liver. Spleen weight index, alanine aminotransferase activity and liver portal venous pressure were also measured. The results showed that anti-fibrosis treatment improved liver fibrosis, splenomegaly, hepatic function, as well as liver portal hypertension. In order to confirm the anti-fibrotic properties of praziquantel, we established a CCL4-induced model and revealed that CCL4-induced liver fibrosis was inhibited by PZQ treatment for 30 days. Furthermore, we analyzed the effects of praziquantel on mouse primary hepatic stellate cells (HSCs). It is indicated that mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9 and TIMP1 of HSCs were all inhibited after praziquantel anti-parasite treatments. Conclusions: The significant amelioration of hepatic fibrosis by praziquantel treatment validates it as a promising drug of anti-fibrosis and offers potential of a new chemotherapy for hepatic fibrosis resulting from schistosomiasis.

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