抗蠕虫药物对致癌肝吸虫 Opisthorchis viverrini 的驱虫活性和病理生理作用。

W Sangkam, P Arunsan, P Pechdee, A Boonsuya, C Thanchonnang, W Chatdumrong, N K Rattanapitoon, S K Rattanapitoon
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引用次数: 0

摘要

在泰国,人类肝吸虫(Opisthorchis viverrini)是导致胆管癌(CCA)的重要风险因素,这主要是由于食用了未煮熟的鲤科鱼类。目前,吡喹酮 (PZQ) 等抗蠕虫药物是治疗 O. viverrini 的主要药物。因此,有必要探索其他抗蠕虫药物对 O. viverrini 的疗效。本研究旨在评估东南亚国家流行地区常用的抗蠕虫药物(PZQ、阿苯达唑(AL)、烟酰胺(NI)和甲苯咪唑(ME),浓度分别为 600、400、500 和 500 毫克/毫升)的疗效。研究还包括用罗斯威尔公园纪念研究所(RPMI)和 PZQ 处理的阴性对照组和阳性对照组。使用 2',7'-二氯荧光素二乙酸酯染色法对表明氧化应激的活性氧(ROS)水平进行量化。使用扫描电子显微镜观察形态变化。此外,还在不同时间点(0、5、30 分钟、1、3、6、12 和 24 小时)进行了运动能力评估,计算相对运动能力(RM)和存活指数(SI)。结果表明,ROS 水平明显增加,虫体荧光强度和校正后的总荧光(CTWF)依次为 PZQ、NI、ME 和 AL。形态学损伤表现为被膜肿胀、乳头变化和微绒毛(Mv)破坏,尤其是在使用最有效的抗蠕虫药 PZQ、NI、ME 和 AL 的组别中,而阴性对照组则没有表现出这些变化。此外,PZQ 处理组抑制成虫蠕动的效果最好,其次分别是 NI、ME 和 AL。总之,第一批新发现表明,除 NI 外,ME 和 AL 有可能成为治疗 O. viverrini 感染的替代疗法。此外,还需要通过动物模型来研究 NI、ME 和 AL 与标准疗法相比的疗效。
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Anthelmintic activity and pathophysiological effect of anthelmintic drugs against carcinogenic liver fluke, Opisthorchis viverrini.

Human liver fluke, Opisthorchis viverrini poses a significant risk for development of cholangiocarcinoma (CCA) in Thailand, primarily attributed to consumption of undercooked cyprinoid fishes. The current use of anthelmintic drug treatment such as praziquantel (PZQ), as the main therapeutic agent against O. viverrini. There is a need to explore the efficacy of alternative anthelmintic drugs for O. viverrini treatment. This study aimed to assess the efficacy of anthelmintic drugs, which are commonly use in endemic areas of Southeast Asian countries; PZQ, albendazole (AL), niclosamide (NI), and mebendazole (ME) at concentrations of 600, 400, 500, and 500 mg/ml. The study included a negative and positive control group treated with roswell park memorial institute (RPMI) and PZQ. Reactive oxygen species (ROS) levels, indicative of oxidative stress, were quantified using 2',7'-dichlorofluorescein diacetate staining. Morphological changes were observed using scanning electron microscopy. Furthermore, motility assessments were conducted at various time points (0, 5, 30 minutes, 1, 3, 6, 12, and 24 hours), calculating relative motility (RM) and survival index (SI). The results revealed a significant increase of ROS levels with the intensity and corrected total worm fluorescence (CTWF) mostly observed in order of PZQ, followed by NI, ME, and AL, respectively. Morphological damage was presented the tegumental swelling, papillae changes, and disruption of microvilli (Mv), particularly in the group treated with the most effective anthelmintics PZQ, NI, ME, and AL, while negative control group did not exhibit such alterations. Also, the most efficacy for suppressing the motility of adult worms were displayed in PZQ treatment group, followed by NI, ME, and AL, respectively. Overall, first novel findings suggest that apart from NI, ME, and AL demonstrate potential as alternative therapeutic options for O. viverrini infection. Furthermore, animal model is needed to investigate the efficacy of NI, ME, and AL compare with standard treatment.

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