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萘普生对淡水水蚤和鱼类的慢性毒性和内分泌干扰作用,以及使用 H295R 细胞检测的类固醇生成改变。

Chronic toxicity and endocrine disruption of naproxen in freshwater waterfleas and fish, and steroidogenic alteration using H295R cell assay.

机构信息

School of Public Health & Institute of Health and Environment, Seoul National University, Seoul, 08826, South Korea.

Department of Occupational and Environmental Health, Yongin University, Yongin, 17092, South Korea.

出版信息

Chemosphere. 2018 Aug;204:156-162. doi: 10.1016/j.chemosphere.2018.04.035. Epub 2018 Apr 7.

Abstract

Naproxen is a non-steroidal anti-inflammatory drug (NSAID) and has been frequently detected in surface waters around the world. Although endocrine disruption and reproduction related effects of NSAIDs are of increasing concern, the ecotoxicity of naproxen in aquatic organisms is limited primarily to acute lethal effects. In this study, chronic toxicity of naproxen was evaluated employing two daphnids (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). The effects of naproxen on sex steroid hormones and gene transcription related to steroidogenesis were also evaluated in H295R cells. The chronic no observed effect concentrations (NOECs) of naproxen for reproduction were determined to be 10 mg L in D. magna and 0.3 mg L in M. macrocopa. At concentrations of 0.5 mg L, the survival of juvenile medaka fish was significantly decreased and transcription of erβ2 gene was significantly increased. Concentration of 17β-estradiol (E2) and the ratio of E2 and testosterone were significantly increased in H295R cells at 10 mg L, suggesting that naproxen could modulate sex hormone production. The current detected levels of naproxen in ambient Korean rivers are far lower than the effective levels, however potential adverse effects cannot be ignored in some highly polluted areas. Endocrine disruption effects in fish warrant further investigation particularly for their ecological implications.

摘要

萘普生是一种非甾体抗炎药(NSAID),已在世界各地的地表水 中频繁检出。尽管 NSAIDs 的内分泌干扰和生殖相关效应引起了越来越多的关注,但萘普生对水生生物的生态毒性主要局限于急性致死效应。在这项研究中,采用两种水蚤(大型溞和蒙古裸腹溞)和一种鱼类(斑马鱼)评估了萘普生的慢性毒性。还在 H295R 细胞中评估了萘普生对与类固醇生成相关的性类固醇激素和基因转录的影响。确定萘普生对繁殖的慢性无观察效应浓度(NOEC)分别为 10mg/L 在大型溞和 0.3mg/L 在蒙古裸腹溞中。在 0.5mg/L 浓度下,幼体斑马鱼的存活率显著降低,erβ2 基因的转录显著增加。在 10mg/L 时,H295R 细胞中的 17β-雌二醇(E2)浓度和 E2 与睾酮的比值显著增加,表明萘普生可以调节性激素的产生。目前在韩国河流环境中检测到的萘普生水平远低于有效水平,但在一些污染严重的地区,不能忽视其潜在的不良影响。鱼类的内分泌干扰效应值得进一步研究,特别是对其生态影响。

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