Praziquantel Protects Acute Liver Injury Induced By Concanavalin A (Con A) In BALB/c Mice

The main damage caused by schistosomiasis japonica is granuloma around theeggs and the liver fibrosis caused by excessive tissues repair in chronic infection. It isreported that the hepatic inflammation in acute stage of schistosomiasis not onlymediates the egg granuloma response but is also the priming of activation in fibrosisassociated cells.As a safe and effective anti-parasite drug, Praziquantel has been used for severaldecades in anti-schistosoma chemotherapy. Recently, some researches suggest thatpraziquantel may have the effect of anti-inflammation and others suggest thatpraziquantel may have the effect of immune regulation. Our previous study found thatpraziquantel treatment significantly inhibited liver inflammatory cytokine andchemokine gene expression levels, play the role in inhibiting inflammatory response,in an schistosomiasis model of mice, which indicated that praziquantel can play asignificant anti-inflammatory role in schistosomiasis mice. If praziquantel hasanti-inflammation effect, new strategy of therapy by using praziquantel will bepossible in treatment of other inflammatory diseases. Accordingly, we evaluatedpraziquantel anti-inflammatory effect in concanavalin A induced acute liver injurymodel of inflammation, expecting to provide experimental basis of praziquantel forclinical treatment and new ideas on liver inflammatory injury.First, we established the mice models of concanavalin A-induced acute liverinjury. The experimental animals were divided into four groups：normal control group,normal praziquantel group, concanavalin A model group and praziquantel group. Weused the experimental methods to detect inflammation-related indicators as follows：H&E stain to evaluate the class of liver damage and liver injury size, collected mouse serum to detect alanine aminotransferase (ALT) and aspartate aminotransferase (AST)by automatic biochemical analyzer; RT-PCR detection for liver and spleeninflammation-related gene expression level; ELISA methods for detection of liverinflammation factor expression level. The aims of this study is to evaluatepraziquantel protection effects on acute hepatic injury induced by concanavalin A.The main results of this study are as follows:1. In praziquantel group the majority of hepatic tissues were similar to the normaltissues histologically, as compared with that of concanavalin A model group. But inconcanavalin A model group, there was a large number of T lymphocyte infiltrationin liver tissues, showing diffuse inflammatory responses. A large number of hepaticcells were ruptured, with fatty degeneration, necrosis and mass cell infiltration oflymphocytes, granulocytes in the tissues. Morphological measurement oninflammatory area showed that in praziquantel group, the inflammatory damage areawas obviously lower than that of concanavalin A model group. The resultdemonstrated that praziquantel can significantly reduce acute liver injury level ofmice induced by concanavalin A.2. Some serum indicators were detected in this study. The results showed that innormal praziquantel group, serum ALT and AST levels were similar to that ofnormal control group, while in the concanavalin A model group ALT and AST levelsincreased significantly, generally up6000U/L. After praziquantel treatment, theydropped dramatically, although still higher than those of the control group. The resultgave further evidence that praziquantel could ameliorate acute liver injury induced byconcanavalin A.3. In order to understand if praziquantel can regulates the expressions ofinflammation-related genes, we detected liver mRNA levels of TNF-α, IFN-γ, CXCL10, CCL3, CCL7and IL-6by using real-time PCR method. The results indicated thatin praziquantel group, all of these inflammation-related cytokines and chemokineswere significantly lower than those in concanavalin A model group. It suggested thatpraziquantel play anti-inflammation effect by down-regulating the expression ofinflammation-related cytokines and chemokines induced by concanavalin A in mice. 4. In order to confirm the effect of praziquantel on inhibiting expression ofinflammation-related cytokines, the liver protein levels of IFN-γ and IL-6wereanalyzed by using ELISA kits. The results showed that in praziquantel group, IFN-γand IL-6expressions showed the tendency to decrease as compared with that ofconcanavalin A model group.In summary, we studied the therapeutic effect of praziquantel on acute liver injurymodel of mice induced by concanavalin A. The results indicated that praziquantelcould ameliorate liver damage induced by concanavalin A by decreasinginflammation-related gene expressions. This study gives new insight into novelapplication of praziquantel on anti-inflammatory responses.