驱虫药物对致癌性肝吸虫 Opisthorchis viverrini 的驱虫活性和病理生理作用。
Anthelmintic activity and pathophysiological effect of anthelmintic drugs against carcinogenic liver fluke, Opisthorchis viverrini.
发表日期:2024 Jun 01
作者:
W Sangkam, P Arunsan, P Pechdee, A Boonsuya, C Thanchonnang, W Chatdumrong, N K Rattanapitoon, S K Rattanapitoon
来源:
Parasites & Vectors
摘要:
人类肝吸虫 Opisthorchis viverrini 对泰国的胆管癌 (CCA) 构成重大风险,这主要归因于食用未煮熟的鲤鱼。目前采用驱虫药物治疗如吡喹酮(PZQ),作为对抗O. viverrini的主要治疗药物。需要探索替代驱虫药物治疗 O. viverrini 的疗效。本研究旨在评估东南亚国家流行地区常用的驱虫药物的功效; PZQ、阿苯达唑 (AL)、氯硝柳胺 (NI) 和甲苯咪唑 (ME),浓度分别为 600、400、500 和 500 mg/ml。该研究包括接受罗斯韦尔公园纪念研究所 (RPMI) 和 PZQ 治疗的阴性和阳性对照组。使用 2',7'-二氯荧光素二乙酸酯染色对指示氧化应激的活性氧 (ROS) 水平进行定量。使用扫描电子显微镜观察形态变化。此外,在不同时间点(0、5、30分钟、1、3、6、12和24小时)进行运动评估,计算相对运动(RM)和生存指数(SI)。结果显示,ROS 水平显着增加,其强度和校正总蠕虫荧光 (CTWF) 主要按 PZQ 的顺序观察到,其次分别是 NI、ME 和 AL。形态学损伤表现为皮膜肿胀、乳头改变和微绒毛破坏(Mv),特别是在用最有效的驱虫药 PZQ、NI、ME 和 AL 治疗的组中,而阴性对照组没有表现出此类改变。此外,PZQ 治疗组对抑制成虫运动的效果最强,其次分别是 NI、ME 和 AL。总体而言,第一个新发现表明,除了 NI 之外,ME 和 AL 也显示出作为 O. viverrini 感染的替代治疗选择的潜力。此外,需要动物模型来研究 NI、ME 和 AL 与标准治疗相比的疗效。
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.