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从生物浓缩的角度看药物代谢物与血液蛋白和膜脂质的相互作用:基于体外评估的初步研究。

Interaction of pharmaceutical metabolites with blood proteins and membrane lipids in the view of bioconcentration: A preliminary study based on in vitro assessment.

机构信息

Department of Environmental Analysis, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.

Department of Environmental Analysis, Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland.

出版信息

Sci Total Environ. 2021 Aug 20;783:146987. doi: 10.1016/j.scitotenv.2021.146987. Epub 2021 Apr 9.

DOI:10.1016/j.scitotenv.2021.146987
PMID:33866166
Abstract

Pharmaceuticals pose a real threat to the environment, which has been proven in many studies to date. However, still little is known about the transformation products (TPs) of these compounds, which can also interact with organisms, causing adverse effects like noticeable toxicity or bioconcentration. Many recent works confirm that metabolites of pharmaceuticals are present in the environment, and preliminary studies suggest that they may be equally dangerous to or even more so than their parent compounds. Additionally, it has been proven that some of them have high hydrolytic stability, thus they may be persistent in the environment. This property also increases the likelihood that these compounds will be uptaken and accumulated in the tissues of organisms. Therefore, the aim of the present study was to preliminarily estimate the affinity of the transformation products of selected drugs for blood proteins and cell membrane-forming lipids, considered as important sorption phases during distribution in a living organism. In this study, it was shown that although the examined metabolites do not have a strong affinity for membrane lipids, they exhibit relatively strong binding to proteins, which may considerably affect the distribution of TPs in an organism and may indicate a non-classical process of bioconcentration. The results obtained confirm that the TPs of pharmaceuticals should be given much more attention and their potential for bioconcentration should be further determined.

摘要

药品对环境构成了真正的威胁,这在迄今为止的许多研究中都得到了证实。然而,人们对这些化合物的转化产物(TPs)知之甚少,这些转化产物也会与生物体相互作用,导致明显的毒性或生物浓缩等不良影响。许多最近的研究工作证实,环境中存在药品的代谢物,初步研究表明,它们可能与母体化合物同样危险,甚至更危险。此外,已经证明其中一些具有很高的水解稳定性,因此它们可能在环境中持久存在。这种特性还增加了这些化合物被生物体组织吸收和积累的可能性。因此,本研究的目的是初步估计选定药物的转化产物与血液蛋白质和细胞膜形成脂质的亲和力,这些物质被认为是在生物体中分布过程中的重要吸附相。在这项研究中,尽管研究的代谢物对膜脂质没有很强的亲和力,但它们对蛋白质表现出相对较强的结合能力,这可能会极大地影响 TPs 在生物体中的分布,并可能表明存在非经典的生物浓缩过程。所得结果证实,应更加关注药品的 TPs,并进一步确定它们的生物浓缩潜力。

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