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代谢组学分析预测了暴露于对乙酰氨基酚的大型溞生长速度的变化。

Metabolomic analysis predicted changes in growth rate in Daphnia magna exposed to acetaminophen.

机构信息

Department of Cell & Systems Biology, University of Toronto, Toronto, Ontario, Canada; Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.

Department of Physical and Environmental Sciences and Environmental NMR Centre, University of Toronto Scarborough, Ontario, Canada; Department of Environmental Science, College of Natural Sciences, Hankuk University of Foreign Studies, 81, Oedae-ro, Mohyeon-eup, Cheoin-gu, Yongin-si, Gyeonggi-do 17035, Republic of Korea.

出版信息

Aquat Toxicol. 2022 Aug;249:106233. doi: 10.1016/j.aquatox.2022.106233. Epub 2022 Jun 25.

DOI:10.1016/j.aquatox.2022.106233
PMID:35779485
Abstract

As urbanization and the global population increases, pollutants associated with municipal wastewater such as pharmaceuticals are becoming more prevalent in aquatic environments. Acetaminophen (paracetamol) is a widely used drug worldwide and one of the most frequently detected pharmaceuticals in freshwater ecosystems. This study investigated the impact of acetaminophen on the metabolite profile of Daphnia magna at two life stages; and used these metabolomic findings to hypothesize a potential impact at a higher organismal level which was subsequently tested experimentally. Targeted polar metabolite analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure changes in the concentration of 51 metabolites in the neonate (> 24 h old) and adult (8 day-old) daphnids following a 48-h exposure to sub-lethal concentrations of acetaminophen. The impact of acetaminophen on the metabolic profile of neonates was widely different from adults. Also, acetaminophen exposure perturbed the abundance of nucleotides more extensively than other metabolites. The acute metabolomic experimental results led to the hypotheses that exposure to sub-lethal concentrations of acetaminophen upregulates protein synthesis in D. magna and subsequently increases growth during early life stages and has an opposite impact on adults. Accordingly, a 10 day growth rate experiment indicated that exposure to acetaminophen elevated biomass production in neonates but not in adults. These novel findings demonstrate that a targeted analysis and interpretation of the changes in the polar metabolic profile of organisms in response to environmental stressors could be used as a tool to predict changes at higher biological levels. As such, this study further emphasizes the incorporation of molecular-level platforms as critical and robust tools in environmental assessment frameworks and biomonitoring of aquatic ecosystems.

摘要

随着城市化和全球人口的增加,与城市废水相关的污染物,如药品,在水生环境中变得越来越普遍。对乙酰氨基酚(扑热息痛)是一种在全球范围内广泛使用的药物,也是淡水生态系统中最常检测到的药物之一。本研究调查了对乙酰氨基酚对两个生命阶段的大型溞代谢物谱的影响;并利用这些代谢组学发现,假设在更高的生物体水平上可能存在潜在影响,随后进行了实验测试。通过液相色谱-串联质谱(LC-MS/MS)进行靶向极性代谢物分析,以测量在亚致死浓度对乙酰氨基酚暴露 48 小时后,新生(>24 小时龄)和成年(8 天龄)溞体内 51 种代谢物浓度的变化。对乙酰氨基酚对新生代谢物谱的影响与成年动物广泛不同。此外,与其他代谢物相比,对乙酰氨基酚暴露更广泛地扰乱了核苷酸的丰度。急性代谢组学实验结果导致了这样的假设,即暴露于亚致死浓度的对乙酰氨基酚会上调大型溞的蛋白质合成,随后在生命早期阶段增加生长,而对成年动物则产生相反的影响。因此,为期 10 天的生长率实验表明,对乙酰氨基酚会增加新生溞的生物量产生,但不会增加成年溞的生物量。这些新发现表明,对生物体对环境胁迫的极性代谢物谱变化进行有针对性的分析和解释,可以作为预测更高生物学水平变化的工具。因此,本研究进一步强调了将分子水平平台作为环境评估框架和水生生态系统生物监测的关键和稳健工具的纳入。

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