Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
Department of Analytical Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
Chemosphere. 2019 Dec;237:124434. doi: 10.1016/j.chemosphere.2019.124434. Epub 2019 Jul 31.
Drugs are potentially dangerous environmental contaminants, as they are designed to have biological effects at low concentrations. Monepantel (MOP), an amino-acetonitrile derivative, is frequently used veterinary anthelmintics, but information about MOP environmental circulation and impact is almost non-existent. We studied the phytotoxicity, uptake and biotransformation of MOP in two fodder plants, Plantago lanceolata and Medicago sativa. The seeds and whole plant regenerants were cultivated with MOP. The plant roots and the leaves were collected after 1, 2, 3, 4, 5 and 6 weeks of cultivation. The lengths of roots and proline concentrations in the roots and leaves were measured to evaluate MOP phytotoxicity. The UHPLC-MS/MS technique with a Q-TOF mass analyser was used for the identification and semi-quantification of MOP and its metabolites. Our results showed no phytotoxicity of MOP. However, both plants were able to uptake, transport and metabolize MOP. Comparing both plants, the uptake of MOP was much more extensive in Medicago sativa (almost 10-times) than in Plantago lanceolate. Moreover, 9 various metabolites of MOP were detected in Medicago sativa, while only 7 MOP metabolites were found in Plantago lanceolata. Based on metabolites structures, scheme of the metabolic pathways of MOP in both plants was proposed. MOP and its main metabolite (MOP sulfone), both anthelmintically active, were present not only in roots but also in leaves that can be consumed by animals. This indicates the potential for undesirable circulation of MOP in the environment, which could lead to many pharmacological and toxicological consequences.
药物是具有潜在危险的环境污染物，因为它们旨在以低浓度产生生物效应。莫能菌素（MOP）是一种氨基乙腈衍生物，常用于兽医驱虫，但有关 MOP 环境循环和影响的信息几乎不存在。我们研究了 MOP 在两种饲料植物，即车前草和紫花苜蓿中的植物毒性、吸收和生物转化。用 MOP 培养种子和整株再生植物。在培养 1、2、3、4、5 和 6 周后，收集植物的根和叶子。测量根的长度和根和叶子中的脯氨酸浓度，以评估 MOP 的植物毒性。使用带有 Q-TOF 质量分析仪的 UHPLC-MS/MS 技术对 MOP 及其代谢物进行鉴定和半定量分析。我们的结果表明 MOP 没有植物毒性。然而，两种植物都能够吸收、运输和代谢 MOP。比较两种植物，紫花苜蓿对 MOP 的吸收要广泛得多（几乎是车前草的 10 倍）。此外，在紫花苜蓿中检测到 9 种 MOP 的代谢物，而在车前草中仅发现 7 种 MOP 代谢物。根据代谢物的结构，提出了 MOP 在两种植物中的代谢途径的方案。具有驱虫活性的 MOP 和其主要代谢物（MOP 亚砜）不仅存在于根部，而且存在于叶子中，这些叶子可以被动物消耗。这表明 MOP 在环境中可能会发生不良循环，这可能会导致许多药理学和毒理学后果。
