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胚胎发育、运动行为、药物对斑马鱼幼虫和胚胎的生化和表观遗传效应,以及在环境现实水平下同时暴露于两种药物时的情况。

Embryonic development, locomotor behavior, biochemical, and epigenetic effects of the pharmaceutical drugs paracetamol and ciprofloxacin in larvae and embryos of Danio rerio when exposed to environmental realistic levels of both drugs.

机构信息

Departamento de Biologia, Universidade de Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.

Centro de Estudos do Ambiente e do Mar, CESAM, Universidade de Aveiro, Campus Universitário de Santiago, Aveiro, Portugal.

出版信息

Environ Toxicol. 2019 Nov;34(11):1177-1190. doi: 10.1002/tox.22819. Epub 2019 Jul 19.

Abstract

For several years, the scientific community has been concerned about the presence of pharmaceuticals in the wild, since these compounds may have unpredictable deleterious effects on living organisms. Two examples of widely used pharmaceuticals that are present in the environment are paracetamol and ciprofloxacin. Despite their common presence in the aquatic environment due to their poor removal by sewage treatment plants, knowledge concerning their putative toxic effects is still scarce. This work aimed to characterize the effects of paracetamol (0.005, 0.025, 0.125, 0.625, and 3.125 mg/L) and ciprofloxacin (0.005, 0.013, 0.031, 0.078, 0.195, and 0.488 μg/L) in zebrafish embryos and larvae, exposed to environmentally relevant levels, close to the real concentrations of these pharmaceuticals in surface waters and effluents. The adopted toxic end points were developmental, a behavioral parameter (total swimming time), and a biomarker-based approach (quantification of the activities of catalase, glutathione-S-transferase, cholinesterases, glutathione peroxidase, and lipid peroxidation levels) combined with epigenetic analysis (immunohistochemical detection of 5-methylcytidine). Exposure to paracetamol had effects on all of the adopted toxic end points; however, ciprofloxacin only caused effects on behavioral tests and alterations in biomarkers. It is possible to ascertain the occurrence of oxidative stress following exposure to both drugs, which was more evident regarding paracetamol, an effect that may be related to the observed epigenetic modifications.

摘要

几年来,科学界一直关注环境中存在的药物,因为这些化合物可能对生物体产生不可预测的有害影响。两种广泛使用的药物,对乙酰氨基酚和环丙沙星,就存在于环境中。尽管由于污水处理厂对它们的去除效果不佳,它们普遍存在于水环境中,但关于它们潜在毒性作用的知识仍然很少。本研究旨在描述在环境相关浓度下,对乙酰氨基酚(0.005、0.025、0.125、0.625 和 3.125mg/L)和环丙沙星(0.005、0.013、0.031、0.078、0.195 和 0.488μg/L)对斑马鱼胚胎和幼鱼的影响,这些浓度接近地表水和废水中这些药物的真实浓度。采用的毒性终点包括发育毒性、行为参数(总游泳时间)和基于生物标志物的方法(过氧化氢酶、谷胱甘肽 S-转移酶、胆碱酯酶、谷胱甘肽过氧化物酶和脂质过氧化水平的活性定量)以及表观遗传分析(5-甲基胞嘧啶的免疫组织化学检测)。暴露于对乙酰氨基酚会对所有采用的毒性终点产生影响;然而,环丙沙星仅对行为测试和生物标志物的改变产生影响。可以确定在暴露于两种药物后都会发生氧化应激,对乙酰氨基酚的这种影响更为明显,这种影响可能与观察到的表观遗传修饰有关。

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