OL-037 Effect of treatment with antifibrotic drugs in combination with PZQ in immunized Schistosoma mansoni infected murine model

The main problem in schistosomal hepatic morbidity is fibrosis and extensive scarring induced by living eggs. In this study, we tried to study the effect of treatment using antihelminthic drug (PZQ) and/or antifibrotic drugs (PTX and silymarin) in combination with immunization. The parasitological parameters, the dynamics of serum-specific immunoglobulins and splenic cytokines associated with changes in granuloma diameter were assessed. Naive mice were immunized intravenously with 10 ug of SEA in three doses at 2 days intervals 6 weeks before infection. Animals were infected by tail immersion with 100 cercariae and divided into several groups. Three groups were treated with PZQ, PTX or silymarin administered alone. Another two groups were treated with PZQ combined with PTX or silymarin. All treated animals and respective controls were sacrificed 12 weeks post infection. Immunization did not affect worm reduction , but slight decrease in granuloma diameter, increase in immunoglobulins and cytokines was observed . Reduction in worm burden was associated with reduction in ova count and changes in oogram pattern which were mainly due to PZQ treatment. Increasing reduction in granuloma diameter, elevation of immunogloulins and cytokines levels were observed in the groups treated with PZQ alone or cmbined with PTX or silymarin. In conclusion, in this study, treatment with PZQ complemented with immunization resulted in significant reduction of parasitological parameters and rise of specific Igs. Addition of antifibrotic drugs PTX or silymarin to PZQ, potentiated an antipathology effect which minimized and ameliorated liver fibrosis by inhibition of HSC activation and accentuation of the effect of suppressor Treg cells. (Journal of American Science 2010; 6(5):208-216). (ISSN: 1545-1003). Key word: Schistosoma mansoni, Praziquantel, Pentoxifyllin, silymarin.