Pattama Prommajun1,2, Jutarop Phetcharaburanin1,2,3, Nisana Namwat1,2, Poramate Klanrit1,2, Prakasit Sa-Ngiamwibool2,4, Malinee Thanee5, Hasaya Dokduang2, Yingpinyapat Kittirat1,2, Jia V Li6, Watcharin Loilome7,2,3. 1. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 2. Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. 3. Khon Kaen University International Phenome Laboratory, Northeastern Science Park, Khon Kaen University, Khon Kaen, Thailand. 4. Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 5. Faculty of Medical Science, Nakhonratchasima College, Nakhon Ratchasima, Thailand. 6. Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, South Kensington Campus, London, U.K. 7. Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; watclo@kku.ac.th.
Abstract
BACKGROUND: Opisthorchis viverrini (Ov) infection-induced 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. Copyright
BACKGROUND: Opisthorchis viverrini (Ov) infection-induced 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. Copyright
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