Development toxicity and stress protein responses in zebrafish embryos after exposure to diclofenac and its solvents, DMSO
Development toxicity and stress protein responses in zebrafish embryos after exposure to diclofenac and its solvents, DMSO
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DOI：
10.1016/j.chemosphere.2004.04.007
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发表时间：
2004-08-01
期刊：
影响因子：
8.8
通讯作者：
Triebskorn, R
中科院分区：
文献类型：
--
作者：
Hallare, AV;Köhler, HR;Triebskorn, R
在环境水样中最常检测到的药物之一是抗风湿药物双氯芬酸。尽管其日益增加的环境意义，关于这种药物对水生物种的早期发育阶段的影响的调查是缺乏到现在为止。为了确定该药物对生长中的鱼胚胎的发育毒性和蛋白毒性，使用DMSO作为溶剂，将斑马鱼卵暴露于6种浓度的双氯芬酸（0、1、20、100、500、1000和2000 μ g-1）。在暴露后48和96小时内，记录并描述了早期生命阶段的参数，如卵和胚胎死亡率、原肠胚形成、体节形成、运动和尾部脱离、色素沉着、心跳和孵化成功率。暴露96小时后，测定双氰胺处理和相应DMSO对照中的应激蛋白（hsp 70）水平。结果显示，所有暴露组在96 h结束前的正常发育中均无显著抑制。然而，有一个延迟的孵化时间胚胎暴露于1000和2000 μ g 1（-1）。晚孵化的胚胎（108小时）没有不同的形态从正常孵化的胚胎。死亡率和平均心率数据没有显示出所有胚胎在敌百虫处理组和DMSO对照组中的显著差异。在整个暴露期间，在所有发育中的胚胎中同样没有观察到明显的畸形。双氯芬酸处理和对照胚胎中的热休克蛋白水平没有显著差异。另一方面，DMSO对照胚胎显示hsp 70水平呈浓度依赖性增加。我们认为双氯芬酸在DMSO触发的应激蛋白表达中可能具有调节作用，这可能对在任何毒性试验中使用DMSO作为溶剂产生影响。由于现有数据表明双氯芬酸未诱导显著的胚胎毒性和蛋白毒性，并且由于本研究中使用的双氯芬酸浓度比环境中检测到的浓度高2000倍，因此该药物不太可能对斑马鱼的早期生命阶段造成危害。(C)2004爱思唯尔有限公司保留所有权利。
One of the most frequently detected pharmaceuticals in environmental water samples is the anti-rheumatic drug, diclofenac. Despite its increasing environmental significance, investigations concerning the effects of this drug on the early developmental stages of aquatic species are lacking up to now. To determine the developmental toxicity and proteotoxicity of this drug on the growing fish embryos, eggs of zebrafish were exposed to six concentrations of diclofenac (0, 1, 20, 100, 500, 1000, and 2000 mug1(-1)) using DMSO as solvent. Early life stage parameters such as egg and embryo mortality, gastrulation, somite formation, movement and tail detachment, pigmentation, heart beat, and hatching success were noted and described within 48- and 96-h of exposure. After the 96-h exposure, the levels of stress proteins (hsp 70) were determined in both the diclofenac-treated and respective DMSO controls. Results showed no significant inhibition in the normal development until the end of 96 h for all exposure groups. However, there was a delay in the hatching time among embryos exposed to 1000 and 2000 mug1(-1). Late-hatched embryos (108 h) did not differ morphologically from normally hatched embryos. The mortality and average heart rate data did not show significant differences for all embryos in both diclofenac-treated and DMSO control groups. No significant malformations were likewise noted among all developing embryos throughout the exposure period. The levels of heat shock proteins in diclofenac- treated and control embryos did not differ significantly. DMSO control embryos, on the other hand, showed a concentration-dependent increase in hsp 70 levels. We suggest possible modulating effect of diclofenac in DMSO-triggered expression of stress proteins and this might have a possible repercussion on the use of DMSO as solvent in any toxicity assay. Since the present data indicate no significant embryotoxicity and proteotoxicity induced by diclofenac and due to the fact that the concentrations of diclofenac used in the present study is up to 2000-fold higher than the concentrations detected in the environment, it is unlikely that this drug would pose a hazard to early-life stages of zebrafish. (C) 2004 Elsevier Ltd. All rights reserved.