BACKGROUND Mekong schistosomiasis is a parasitic disease caused by the blood-dwelling fluke Schistosoma mekongi. This disease contributes to human morbidity and mortality in the Mekong region, posing a public health threat to people in the area. Currently, praziquantel (PZQ) is the drug of choice for the treatment of Mekong schistosomiasis. However, the molecular mechanisms of PZQ action remain unclear, and Schistosoma PZQ resistance has been reported occasionally. Through this research, we aimed to use a metabolomic approach to identify the potentially altered metabolic pathways in S. mekongi associated with PZQ treatment. METHODOLOGY/PRINCIPAL FINDINGS Adult stage S. mekongi were treated with 0, 20, 40, or 100 μg/mL PZQ in vitro. After an hour of exposure to PZQ, schistosome metabolites were extracted and studied with mass spectrometry. The metabolomic data for the treatment groups were analyzed with the XCMS online platform and compared with data for the no treatment group. After low, medium (IC50), and high doses of PZQ, we found changes in 1,007 metabolites, of which phosphatidylserine and anandamide were the major differential metabolites by multivariate and pairwise analysis. In the pathway analysis, arachidonic acid metabolism was found to be altered following PZQ treatment, indicating that this pathway may be affected by the drug and potentially considered as a novel target for anti-schistosomiasis drug development. CONCLUSIONS/SIGNIFICANCE Our findings suggest that arachidonic acid metabolism is a possible target in the parasiticidal effects of PZQ against S. mekongi. Identifying potential targets of the effective drug PZQ provides an interesting viewpoint for the discovery and development of new agents that could enhance the prevention and treatment of schistosomiasis.

中文翻译：

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代谢组学揭示了接触吡喹酮后湄公河血吸虫花生四烯酸代谢的变化。

背景技术湄公河血吸虫病是由寄生于血吸虫的湄公河血吸虫引起的一种寄生虫病。这种疾病会导致湄公河地区的人类发病率和死亡率上升，对该地区人民的公共卫生构成威胁。目前，吡喹酮（PZQ）是治疗湄公河血吸虫病的首选药物。然而，PZQ 作用的分子机制尚不清楚，偶尔有报道称血吸虫 PZQ 耐药。通过这项研究，我们旨在使用代谢组学方法来确定与 PZQ 治疗相关的湄公河豚中潜在改变的代谢途径。方法学/主要发现 在体外用 0、20、40 或 100 μg/mL PZQ 处理成年湄公河豚鼠。暴露于 PZQ 一小时后，提取血吸虫代谢物并用质谱法研究。使用 XCMS 在线平台分析治疗组的代谢组学数据，并与未治疗组的数据进行比较。在低、中 (IC50) 和高剂量的 PZQ 后，我们发现 1,007 种代谢物发生变化，其中磷脂酰丝氨酸和 anandamide 是多变量和成对分析的主要差异代谢物。在通路分析中，发现花生四烯酸代谢在 PZQ 治疗后发生改变，表明该通路可能受到药物的影响，并有可能被视为抗血吸虫病药物开发的新靶点。结论/意义我们的研究结果表明，花生四烯酸代谢是 PZQ 对湄公河链球菌的杀寄生虫作用的可能目标。