In vitro analysis of inflammatory responses following environmental exposure to pharmaceuticals and inland waters
In vitro analysis of inflammatory responses following environmental exposure to pharmaceuticals and inland waters
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DOI：
10.1016/j.scitotenv.2008.10.016
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发表时间：
2009-02-01
影响因子：
9.8
通讯作者：
Olsson, Per-Erik
中科院分区：
文献类型：
--
作者：
Khalaf, Hazem;Salste, Lotta;Olsson, Per-Erik
药物定期释放到环境中;特别是非甾体抗炎药（NSAID）和抗生素。据报告，红霉素、萘普生、呋塞米和阿替洛尔在环境中可稳定长达1年，这增加了蓄积风险。在本研究中，我们已经测量了发生和浓度的药物在河流Viskan（Jossabron）下游的污水处理厂在Boras，瑞典。通过使用人T24膀胱上皮细胞和Jurkat T细胞评价炎症反应（NF-κ B和AP-1），检测药物和水样的潜在人体风险。T24细胞中的NF-κ B活性被分析的所有NSAID（双氯芬酸、酮洛芬、萘普生、布洛芬和异丙氧芬）显著降低，但也被甲氧苄啶（使用环境相关浓度）显著降低。NF-κ B和AP-1的激活进一步分析响应于从瑞典不同地点收集的水样。在所有位置观察到Jurkat细胞中AP-1活性的剂量依赖性下调。在两个位置（Jossabron和Almenas）观察到NF-κ B下调。与此相反，NF-κ B反应加强暴露于水从两个位置后，NF-κ B活化处理热灭活大肠杆菌。为了确定药物参与应答，基于Jossabron测定的水平，将T24细胞暴露于药物混合物。这导致在单独暴露于药物混合物后NF-κ B应答降低，而当细胞共同暴露于热灭活的E.大肠杆菌和药物。所获得的结果表明，所鉴定的药物影响炎症反应，并且还表明存在具有增强炎症反应能力的未知物质。(C)2008 Elsevier B. V.保留所有权利。
Pharmaceuticals are regularly released into the environment; in particular non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Erythromycin, naproxen, furosemide and atenolol are reported to be stable for up to 1 year in the environment, which increases the risk for accumulation. In the present study we have measured the occurrence and concentration of phannaceuticals in river Viskan (Jossabron) downstream of a sewage treatment plant in Boras, Sweden. Pharmaceuticals and water samples were tested for potential human risk by evaluating inflammatory responses (NF-kappa B and AP-1) using human T24 bladder epithelial cells and Jurkat T-cells. NF-kappa B activity in T24 cells was significantly reduced by all NSAIDs analysed (diclofenac, ketoprofen, naproxen, ibuprophen and dextropropoxyphene), but also by trimethoprim, using environmentally relevant concentrations. NF-kappa B and AP-1 activation was further analysed in response to water samples collected from different locations in Sweden. Dose-dependent down-regulation of AP-1 activity in Jurkat cells was observed at all locations. At two locations (Jossabron and Almenas) down-regulation of NF-kappa B was observed. In contrast, the NF-kappa B response was potentiated by exposure to water from both locations following activation of NF-kappa B by treatment with heat-killed Escherichia coli. To determine the involvement of pharmaceuticals in the responses, T24 cells were exposed to the pharmaceutical mixture, based on the determined levels at Jossabron. This resulted in reduction of the NF-kappa B response following exposure to the pharmaceutical mixture alone while no potentiation was observed when cells were co-exposed to heat killed E. coli and pharmaceuticals. The obtained results demonstrate that the identified pharmaceuticals affect the inflammatory responses and furthermore indicate the presence of unknown substance(s) with the ability to potentiate inflammatory responses. (C) 2008 Elsevier B.V. All rights reserved.