Pharmaceuticals have been considered as emerging organic contaminants in the environment that might pose huge risk to the non-target aquatic organisms. Mianserin, a tetracyclic antidepressant, is present at low detectable concentrations in the aquatic environment; however, limited attention has been devoted to its potential adverse effects on the aquatic animals. In the present study, we first performed an acute toxicity test for mianserin exposure using zebrafish (Danio rerio) embryos during 4–124 h post fertilization (hpf). Time-dependent lethal concentrations of mianserin exposure on the zebrafish embryos were firstly determined at mg/L levels. Then, a series of sublethal concentrations of 0.01, 0.1, 1, 10, 100, and 1000 μg/L of mianserin were prepared for the short-term exposure of zebrafish embryos for 120 h. The results showed that mianserin exposure reduced the body length of zebrafish larvae, in addition to altering multiple physiological and biochemical parameters in the exposed embryos/larvae. A dose-dependent inhibition of the total antioxidant capacity and total cholinesterase activity was revealed in the exposed fish larvae upon increasing the concentrations of mianserin exposure. A U-shaped concentration-dependent response curve was observed for the adrenocorticotropic hormone; however, an inversed U-shaped response curve was obtained for the monoamine oxidase level in response to mianserin exposure. Activities of the total adenosine triphosphatase (T-ATPase), Na⁺/K⁺-ATPase, and Ca²⁺/Mg²⁺-ATPase were significantly increased in the fish larvae exposed to relatively high doses of mianserin; interestingly however, low dose of mianserin at 10 ng/L inhibited their Na⁺/K⁺-ATPase and T-ATPase activities. Additionally, the coordinated regulation of cyclic adenosine monophosphate and protein kinase A was observed in the mianserin-exposed fish larvae, implying a reserved signaling pathway involved in the fish response to the antidepressant. Therefore, our study demonstrated that mianserin exposure significantly affected the early development of fish embryos at environmentally relevant concentrations, and suggested that the risk of pharmaceutical contamination of the aquatic environment, even at low doses, should receive more attention.

药物被认为是环境中的新兴有机污染物，可能会对非目标水生生物造成巨大风险。四环抗抑郁药Mianserin在水生环境中的含量低，可检测到。然而，人们对其潜在的不利影响仅限于关注其对水生动物的危害。在本研究中，我们首先使用斑马鱼（Danio rerio）对米安色林暴露进行了急性毒性试验）受精（hpf）后4–124小时内的胚胎。首先确定了斑马鱼胚胎中棉安素暴露的时间依赖性致死浓度（mg / L）。然后，制备了一系列浓度为0.01、0.1、1、10、100和1000μg/ L的米安色林亚致死浓度，用于斑马鱼胚胎的短期暴露120 h。结果表明，棉安素暴露减少了斑马鱼幼虫的体长，此外还改变了暴露的胚胎/幼虫的多个生理和生化参数。随着mianerin暴露浓度的增加，在暴露的鱼幼虫中发现了总抗氧化剂能力和总胆碱酯酶活性的剂量依赖性抑制。观察到促肾上腺皮质激素呈U形的浓度依赖性反应曲线。然而，响应米安色林暴露，获得了单胺氧化酶水平的倒U形响应曲线。总腺苷三磷酸酶（T-ATPase）的活性，Na在暴露于较高剂量棉仁素的鱼幼虫中，⁺ / K ⁺ -ATPase和Ca ²⁺ / Mg ²⁺ -ATPase显着增加。有趣的是，低剂量的mianserin浓度为10 ng / L会抑制其Na ⁺ / K ⁺-ATPase和T-ATPase活性。另外，在暴露于棉塞林的鱼幼虫中观察到环状腺苷单磷酸和蛋白激酶A的协调调节，这暗示了鱼对抗抑郁药的反应中存在一个保留的信号通路。因此，我们的研究表明，在环境相关浓度下，米安色林暴露会显着影响鱼胚胎的早期发育，并建议即使在低剂量下，水生环境药物污染的风险也应引起更多关注。