Metabolic profiling of praziquantel-mediated prevention of opisthorchis viverrini-induced cholangiocyte transformation in the hamster model of cholangiocarcinoma

Abstract

Background: Opisthorchis viverrini (Ov) infectioninduced cholangiocarcinoma (CCA) is a major public health problem in northeastern Thailand. Praziquantel was shown to prevent CCA development in an Ov-infected hamster model; however, the molecular mechanism remains unknown. Materials and Methods: In this study, we used a hamster model with Ov and N-nitrosodimethylamine-induced CCA to study the mechanisms of praziquantel action. The liver tissues from the hamsters with and without praziquantel treatment were analyzed using 1H nuclear magnetic resonance spectroscopy. Results: A total of 14 metabolites were found to be significantly different between the two groups. Furthermore, the combination of acetate, inosine and sarcosine was shown to exert an anti-inflammatory effect through interleukin-6 inhibition in a macrophage cell line, suggesting a mechanism by which praziquantel may prevent inflammation caused by Ov, cholangiocyte transformation and further CCA develpoment. Conclusion: These findings might avail the development of a preventive strategy for CCA in high-risk populations.