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白腐真菌糙皮侧耳对拉莫三嗪的转化。

Transformation of lamotrigine by white-rot fungus Pleurotus ostreatus.

机构信息

Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel.

Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 7610001, Israel.

出版信息

Environ Pollut. 2019 Jul;250:546-553. doi: 10.1016/j.envpol.2019.04.057. Epub 2019 Apr 12.

DOI:10.1016/j.envpol.2019.04.057
PMID:31026702
Abstract

One of the most persistent pharmaceutical compounds commonly found in treated wastewater is lamotrigine (LTG). It has also been detected in soils and crops irrigated with treated wastewater. Here we focused on the ability of the white-rot edible mushroom Pleurotus ostreatus to remove and transform LTG in liquid cultures. At concentrations of environmental relevance (1 and 10 μg L) LTG was almost completely removed from the culture medium within 20 days. To elucidate the mechanism of LTG removal and transformation, we applied a physiological-based approach using inhibitors and a competing agent. These experiments were conducted at a higher concentration for metabolites detection. Based on identification of sulfur-containing metabolites and LTG N2-oxide and the effect of specific inhibitors, cytochrome P450 oxidation is suggested as one of the reaction mechanisms leading to LTG transformation. The variety and number of transformation products (i.e., conjugates) found in the current study were larger than reported in mammals. Moreover, known conjugates with glucuronide, glutathione, or cysteine/glycine, were not found in our system. Since the majority of the identified transformation products were conjugates of LTG, this study highlights the persistence of LTG as an organic pollutant in ecosystems exposed to wastewater.

摘要

一种在处理后的废水中经常发现的最持久的药物化合物是拉莫三嗪 (LTG)。它也在经过处理的废水灌溉的土壤和作物中被检测到。在这里,我们专注于白腐可食用蘑菇糙皮侧耳(Pleurotus ostreatus)在液体培养中去除和转化 LTG 的能力。在环境相关浓度(1 和 10μg/L)下,LTG 在 20 天内几乎完全从培养基中去除。为了阐明 LTG 去除和转化的机制,我们使用抑制剂和竞争剂应用了基于生理的方法。这些实验在更高的浓度下进行,以检测代谢物。基于含硫代谢物和 LTG N2-氧化物的鉴定以及特定抑制剂的作用,细胞色素 P450 氧化被认为是导致 LTG 转化的反应机制之一。本研究中发现的转化产物(即缀合物)的种类和数量比哺乳动物中报道的要多。此外,在我们的系统中没有发现与葡萄糖醛酸、谷胱甘肽或半胱氨酸/甘氨酸缀合的已知缀合物。由于大多数鉴定出的转化产物是 LTG 的缀合物,因此本研究强调了在暴露于废水的生态系统中,LTG 作为有机污染物的持久性。

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