School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.
Shanghai Applied Radiation Institute, Shanghai University, Shanghai 200444, China.
Aquat Toxicol. 2014 Jun;151:68-76. doi: 10.1016/j.aquatox.2013.12.029. Epub 2014 Jan 8.
Amitriptyline is a tricyclic antidepressant used for decades. It is present at low detectable concentrations in the aquatic environment, but relative few studies have focused on its ecotoxicological effects on non-target aquatic animals. The present study conducted an acute toxicity test of waterborne amitriptyline exposure using zebrafish (Danio rerio) embryos 4 to 124 h-post-fertilization. Time-dependent lethal concentrations were firstly determined and at mg/L levels. Effects of amitriptyline on zebrafish embryos were then evaluated under amitriptyline exposure at sublethal concentrations of 1, 10, 100 ng/L, 1, 10, 100 μg/L and 1mg/L. Our results showed that amitriptyline significantly reduced the hatching time and body length of embryos after exposure in a concentration-dependent manner. Our study also revealed that the exposure evoked a coordinated modulation of physiological and biochemical parameters in exposed zebrafish embryos, including alterations of adrenocorticotropic hormone (ACTH) level, oxidative stress and antioxidant parameters, as well as nitric oxide (NO) production and total nitric oxide synthase (TNOS) activity. A U-shaped concentration-dependent response curve was observed in ACTH level in response to amitriptyline exposure. However, both U-shaped and inversed U-shaped curves were indicated in the responses of antioxidant parameters, including total antioxidant capacity, antioxidant enzyme activities (catalase, superoxide dismutase and peroxidase), glutathione content and glutathione reductase activity. Correspondingly, hydroxyl radical formation and lipid peroxidation indices changed in similar U-shaped concentration-dependent patterns, which together the results of antioxidant parameters suggested induction of oxidative stress in embryos exposed to amitriptyline at high concentrations. Moreover, NO production and TNOS activity were both significantly affected by amitriptyline exposure. Notably, significant correlations between these measured parameters were revealed, which suggested a dynamic adaptation process and coordinated regulation of multiple physiological systems in fish embryos to amitriptyline treatment. Furthermore, our study demonstrated that the effective concentrations of amitriptyline for measured parameters in zebrafish embryos were as low as 10 ng/L, and thus revealed the potential risk of amitriptyline and other antidepressants to aquatic life.
阿米替林是一种三环类抗抑郁药，已经使用了几十年。它在水生环境中以低检测浓度存在，但相对较少的研究集中在它对非目标水生动物的生态毒理学影响上。本研究采用斑马鱼（Danio rerio）胚胎 4 至 124 小时受精后进行了水基阿米替林暴露的急性毒性试验。首先确定了与时间相关的致死浓度，并达到了毫克/升的水平。然后在亚致死浓度 1、10、100ng/L、1、10、100μg/L 和 1mg/L 下评估了阿米替林对斑马鱼胚胎的影响。我们的结果表明，阿米替林以浓度依赖的方式显著降低了胚胎的孵化时间和体长。我们的研究还表明，暴露引起了暴露的斑马鱼胚胎中生理和生化参数的协调调节，包括促肾上腺皮质激素（ACTH）水平、氧化应激和抗氧化参数以及一氧化氮（NO）产生和总一氧化氮合酶（TNOS）活性的改变。在对阿米替林暴露的反应中，ACTH 水平呈 U 形浓度依赖性响应曲线。然而，抗氧化参数的反应呈 U 形和倒 U 形曲线，包括总抗氧化能力、抗氧化酶活性（过氧化氢酶、超氧化物歧化酶和过氧化物酶）、谷胱甘肽含量和谷胱甘肽还原酶活性。相应地，羟基自由基形成和脂质过氧化指数呈相似的 U 形浓度依赖性模式变化，这些结果与抗氧化参数一起表明，在高浓度下暴露于阿米替林的胚胎中诱导了氧化应激。此外，NO 产生和 TNOS 活性均受阿米替林暴露的显著影响。值得注意的是，这些测量参数之间存在显著相关性，这表明在鱼胚胎中存在一个动态适应过程和多个生理系统的协调调节来对抗阿米替林的处理。此外，我们的研究表明，阿米替林在斑马鱼胚胎中对测量参数的有效浓度低至 10ng/L，从而揭示了阿米替林和其他抗抑郁药对水生生物的潜在风险。
