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 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: