title: New insight into the antifibrotic effects of praziquantel on mice in infection with Schistosoma japonicum.
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.
  
  
  RESULTS
  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 CCL(4)-induced model and revealed that CCL(4)-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.
authors.affiliation: Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Liang
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.forename: Dan
authors.initials: D
authors.lastname: Zheng
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Chen
authors.forename: Yong-Ya
authors.initials: YY
authors.lastname: Ren
authors.forename: Ke-Yi
authors.initials: KY
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhao-Song
authors.initials: ZS
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D011223:Praziquantel / Q000627:therapeutic use*; D012549:Schistosoma japonicum / Q000187:drug effects / Q000472:pathogenicity*; D012554:Schistosomiasis japonica / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000871:Anthelmintics; D011223:Praziquantel; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006909:Hydroxyproline