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Identification of plumbagin as an effective chemotherapeutic agent for treatment of Gyrodactylus infections
Aquaculture ( IF 4.5 ) Pub Date : 2021-01-11 , DOI: 10.1016/j.aquaculture.2021.736372
Xiao Tu , Chenxi Duan , Siwei Wu , Shengli Fu , Jianmin Ye

Monogenean parasites are responsible for severe economic losses of both freshwater and marine aquaculture industries. Current chemotherapeutic treatments are consuming, expensive, and harmful to water quality and human health. Medicinal plants are a reliable source of alternative anthelmintic agents. In the pursuit of novel anti-monogenean drugs, in vivo anthelminthic efficacy of 26 selected phytochemical compounds was studied, by choosing Gyrodactylus kobayashi infecting goldfish (Carassius auratus) as a model. The screening results showed that four compounds (plumbagin (PLB), thymoquinone, osthole and psoralen) had the highest activity against G. kobayashii with EC99 value ranging from 0.4 to 4.0 mg/L after 48-h exposure. Among these active compounds, PLB was the most efficacious one and selected for the next study. In vitro trials revealed the clear anti-parasitic effects of PLB, with complete death at 45 min of exposure at a concentration of 2.0 mg/L, withdrawal of PLB afterward did not lead to the recovery of the exposed parasites. Bathing G. kobayashii infected goldfish in PLB also significantly reduced the worm burden, with an extremely low EC50 value of 0.09 mg/L after 48-h immersion. The results also showed that one short bath using very low concentrations of 0.4–0.7 mg/L for 30–60 min was effective in eliminating G. kobayashii infection with no visible fish toxicity. Acute toxicity assay indicated the 48-h LC50 of PLB against goldfish was 0.657 mg/L. Furthermore, SEM analysis displayed that PLB-mediated worm killing was associated with the tegumental damages. As seen by TEM, in vivo treatment against G. kobayashii with PLB also caused vacuolization and lysis of parasite's tegument, besides, differing degrees of damage to vitelline cells were observed in treated worms. Collectively, simple chemical structure along with the potent efficacy demonstrated that PLB could serve as an ideal leading compound in the development of a commercial drug to control Gyrodactylus infections in aquaculture



中文翻译:

鉴定铅蛋白可作为一种有效的化学疗法治疗绞股蓝线虫感染

单基因寄生虫是造成淡水和海水养殖业严重经济损失的原因。当前的化学治疗方法消耗,昂贵并且对水质和人体健康有害。药用植物是替代驱虫药的可靠来源。为了追求新型抗单基因药物,通过选择感染小鱼假单胞菌的金鱼(Carassius auratus)为模型,研究了26种选择的植物化学化合物的体内驱虫药功效。筛选结果表明,四种化合物(白花丹素(PLB),百里醌,蛇床子素和补骨脂素)具有针对最高的活性G. kobayashii与EC 99暴露48小时后的值在0.4至4.0 mg / L之间。在这些活性化合物中,PLB是最有效的化合物,并被选择用于下一个研究。体外试验显示,PLB具有明显的抗寄生虫作用,在浓度为2.0 mg / L的暴露45分钟时会完全死亡,之后撤回PLB不会导致暴露的寄生虫恢复。沐浴G. kobayashii在PLB感染金鱼也显著降低蜗杆负担,以极低的EC 50后48小时浸没的0.09毫克/ L值。结果还表明,使用0.4-0.7 mg / L极低浓度的30分钟至60分钟的短浴可有效消除小林石G感染,没有可见的鱼类毒性。急性毒性试验表明,PLB对金鱼的48小时LC 50为0.657 mg / L。此外,SEM分析表明,PLB介导的蠕虫杀死与外皮损伤有关。如通过TEM所见,用PLB在体内对小林志贺氏菌的体内处理也引起寄生虫的皮囊的空泡化和溶解,此外,在处理过的蠕虫中观察到对卵黄细胞的不同程度的破坏。总的来说,简单的化学结构以及强大的功效证明,PLB可作为开发用于控制水产养殖中的陀螺感染的商业药物的理想领先化合物

更新日期:2021-01-16
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