Laboratory of Veterinary Clinical Parasitology, Department of Veterinary Medicine, Federal University of Paraná, Curitiba, Paraná 80035-050, Brazil.
Laboratory of Chemical and Enzymatic Synthesis, Department of Chemistry, Federal University of Paraná, Curitiba, Paraná 81531-980, Brazil.
Acta Trop. 2024 Oct;258:107363. doi: 10.1016/j.actatropica.2024.107363. Epub 2024 Aug 15.
Fasciolosis is a food and waterborne disease caused by Fasciola spp., representing a global health burden to various hosts, including humans and other animals. This study investigates the in vitro activity of tellurium- and selenium-containing diaryl dichalcogenides: diacetal ditelluride (LQ07), diacetal diselenide (LQ62), and diacetyl diselenide (LQ68) alone and in combination with ivermectin (IVM) against eggs of Fasciola hepatica. The eggs were exposed for 12 h with each organochalcogen (OC) (0.1 - 2 mmol l) and IVM (0.01 - 2 mmol l) following an incubation of 15 days, allowing embryonation. The inhibitory concentration of 50 % (IC) of each OC or IVM was tested with the IC, IC, and IC of IVM or each OC, respectively. LQ07, LQ62, and LQ68, as well as IVM, demonstrated a concentration-dependent ovicidal activity. The peak ovicidal activity of 99.74 % was achieved when IVM was tested at 2.0 mmol l. LQ62 and LQ68 demonstrated greater ovicidal activity, having an IC < 0.32 mmol l being 6.25-fold more toxic than IVM alone. The percentage of dead eggs was significantly higher in the IVM group (early mortality), as Se-containing OCs led to the (miracidia) embryonation of the eggs with no hatching (late mortality). Blending Se-containing OCs and IVM showed an additive effect of up to 27 % against F. hepatica eggs. The present data contribute to the potential use of blending-based therapeutic strategies to combat F. hepatica infections in eradication programs worldwide. The combinations may also act against multidrug-resistant strains, reinstating drug-based parasite control.
肝片吸虫病是一种食源性和水源性疾病，由 Fasciola 属引起，给包括人类和其他动物在内的各种宿主带来了全球健康负担。本研究调查了含碲和硒的二芳基二硫代杂环戊烯：二缩醛二碲化物 (LQ07)、二缩醛二硒化物 (LQ62) 和二乙酰二硒化物 (LQ68) 单独使用以及与伊维菌素 (IVM) 联合使用对肝片吸虫卵的体外活性。在孵育 15 天后，用每种有机碲化合物 (OC) (0.1-2 mmol l) 和 IVM (0.01-2 mmol l) 暴露卵 12 h，允许胚胎发育。用各 OC 或 IVM 的 IC、IC 和 IC 测试每种 OC 或 IVM 的 IC 的 50%抑制浓度 (IC)。LQ07、LQ62 和 LQ68 以及 IVM 均表现出浓度依赖性杀卵活性。当 IVM 在 2.0 mmol l 时，达到 99.74%的峰值杀卵活性。LQ62 和 LQ68 表现出更强的杀卵活性，IC < 0.32 mmol l，比单独使用 IVM 毒性高 6.25 倍。IVM 组的死卵百分比明显更高（早期死亡率），而含硒 OC 导致卵的（毛蚴）胚胎发育但无孵化（晚期死亡率）。含硒 OC 和 IVM 的混合显示对 F. hepatica 卵的加性效应高达 27%。本数据有助于基于混合的治疗策略在全球根除计划中用于防治肝片吸虫感染。这些组合还可能对抗多药耐药株，恢复基于药物的寄生虫控制。
