Näslund Johanna, Fick Jerker, Asker Noomi, Ekman Elisabet, Larsson D G Joakim, Norrgren Leif
Section of Pathology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Department of Chemistry, Umeå University, Umeå, Sweden.
Aquat Toxicol. 2017 Aug;189:87-96. doi: 10.1016/j.aquatox.2017.05.017. Epub 2017 May 31.
Diclofenac, a commonly used non-steroidal anti-inflammatory drug, is considered for regulation under the European water framework directive. This is because effects on fish have been reported at concentrations around those regularly found in treated sewage effluents (∼1μg/L). However, a recent publication reports no effects on fish at 320μg/L. In this study, three-spined sticklebacks (Gasterosteus aculeatus) were exposed to 0, 4.6, 22, 82 and 271μg/L diclofenac in flow-through systems for 28days using triplicate aquaria per concentration. At the highest concentration, significant mortalities were observed already after 21days (no mortalities found up to 22μg/L). Histological analysis revealed a significant increase in the proportion of renal hematopoietic tissue (renal hematopoietic hyperplasia) after 28days at the lowest concentration and at all higher concentrations, following a clear dose-response pattern. Skin ulcerations of the jaw were noted by macroscopic observations, primarily at the two highest concentrations. No histological changes were observed in the liver. There was an increase in the relative hepatic mRNA levels of c7 (complement component 7), a gene involved in the innate immune system, at 22μg/L and at all higher concentrations, again following a clear dose-response. The bioconcentration factor was stable across concentrations, but lower than reported for rainbow trout, suggesting lower internal exposure to the drug in the stickleback. In conclusion, this study demonstrates that diclofenac causes histological changes in the three-spined stickleback at low μg/L concentrations, which cause concern for fish populations exposed to treated sewage effluents.
双氯芬酸是一种常用的非甾体抗炎药，正考虑根据欧洲水框架指令进行监管。这是因为在经处理的污水排放物中经常发现的浓度（约1μg/L）左右已报告对鱼类有影响。然而，最近的一篇出版物报道在320μg/L时对鱼类没有影响。在本研究中，将三刺鱼（Gasterosteus aculeatus）置于流通系统中，分别暴露于0、4.6、22、82和271μg/L的双氯芬酸环境中28天，每个浓度设置三个重复水族箱。在最高浓度下，仅21天后就观察到显著的死亡率（在22μg/L及以下未发现死亡情况）。组织学分析显示，在最低浓度及所有更高浓度下，28天后肾造血组织比例显著增加（肾造血组织增生），呈现明显的剂量反应模式。通过宏观观察发现下颌皮肤溃疡，主要出现在两个最高浓度组。肝脏未观察到组织学变化。在22μg/L及所有更高浓度下，参与先天免疫系统的基因c7（补体成分7）的肝脏相对mRNA水平增加，同样呈现明显的剂量反应。生物富集因子在各浓度下稳定，但低于虹鳟鱼的报告值，表明三刺鱼体内对该药物的内部暴露较低。总之，本研究表明双氯芬酸在低μg/L浓度下会导致三刺鱼出现组织学变化，这对暴露于经处理污水排放物中的鱼类种群构成担忧。
