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贝类细胞对β受体阻断类药物体外暴露的响应。

Cellular responses to in vitro exposures to β-blocking pharmaceuticals in hard clams and Eastern oysters.

机构信息

National Research Council Postdoctoral Research Associate, Narragansett, RI, USA.

US Environmental Protection Agency, ORD-NHEERL, Atlantic Ecology Division, Narragansett, RI, USA.

出版信息

Chemosphere. 2018 Nov;211:360-370. doi: 10.1016/j.chemosphere.2018.07.156. Epub 2018 Jul 27.

DOI:10.1016/j.chemosphere.2018.07.156
PMID:30077932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6158783/
Abstract

Increased consumption and improper disposal of prescription medication, such as beta (β)-blockers, contribute to their introduction into waterways and may pose threats to non-target aquatic organisms. There has been rising concern about the impacts of these prescription drugs on coastal ecosystems, especially because wastewater treatment plants are not designed to eliminate them from the discharge. Few studies have characterized the sublethal effects of β-blocker exposures in marine invertebrates. The overall aim of our research is to identify cellular responses of two commercially important filter-feeding marine bivalves, hard clams (Mercenaria mercenaria) and Eastern oysters (Crassostrea virginica), upon exposures to two β-blocker drugs, propranolol and metoprolol. In vitro exposures with bivalve digestive gland and gill tissues were conducted where tissues were separately exposed to each drug for 24 h. Tissue samples were analyzed for cellular damage (lysosomal membrane destabilization and lipid peroxidation), total antioxidant capacity, and glutathione-s-transferase activity. Elevated damage and changes in enzyme activities were noted in the exposed tissues at environmentally relevant concentrations. Differences in species and tissue sensitivities and responses to exposures were also observed. These studies enhance our understanding of the potential impacts of prescription medication on coastal organisms. Additionally, this work demonstrates that filter-feeders may serve as good model organisms to examine the effects of unintended environmental exposures to β-blockers. These studies are part of our ongoing work aimed at evaluation of sublethal biomarkers of pharmaceutical exposures and identification of key events that can contribute to the development of adverse outcome pathways (AOPs).

摘要

处方药(如β-受体阻滞剂)的消耗增加和处理不当导致其进入水道,并可能对非目标水生生物构成威胁。人们越来越关注这些处方药对沿海生态系统的影响,特别是因为污水处理厂没有设计将它们从排放物中消除。很少有研究描述了β-受体阻滞剂暴露对海洋无脊椎动物的亚致死影响。我们研究的总体目标是确定两种具有商业重要性的滤食性海洋双壳贝类(硬壳蛤(Mercenaria mercenaria)和东方牡蛎(Crassostrea virginica))在暴露于两种β-受体阻滞剂药物(普萘洛尔和美托洛尔)时的细胞反应。在体外,用双壳贝类消化腺和鳃组织进行暴露实验,其中组织分别暴露于每种药物 24 小时。分析组织样品的细胞损伤(溶酶体膜不稳定和脂质过氧化)、总抗氧化能力和谷胱甘肽-S-转移酶活性。在环境相关浓度下,暴露组织中观察到细胞损伤和酶活性的升高。还观察到物种和组织敏感性以及对暴露的反应存在差异。这些研究增强了我们对处方药物对沿海生物潜在影响的理解。此外,这项工作表明,滤食性动物可以作为很好的模型生物,用于研究β-受体阻滞剂对环境暴露的影响。这些研究是我们正在进行的工作的一部分,旨在评估药物暴露的亚致死生物标志物,并确定可能导致不良结果途径(AOP)发展的关键事件。

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