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环境相关浓度氟西汀诱导的氧化应激对斑马鱼胚胎发育的影响。

Effects of oxidative stress induced by environmental relevant concentrations of fluoxetine on the embryonic development on Danio rerio.

机构信息

Laboratorio de Toxicología Ambiental, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón intersección Paseo Tollocan, Colonia Residencial Colón, CP 50120 Toluca, Estado de México, Mexico.

Laboratorio de Toxicología Ambiental, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón intersección Paseo Tollocan, Colonia Residencial Colón, CP 50120 Toluca, Estado de México, Mexico.

出版信息

Sci Total Environ. 2022 Feb 10;807(Pt 3):151048. doi: 10.1016/j.scitotenv.2021.151048. Epub 2021 Oct 18.

DOI:10.1016/j.scitotenv.2021.151048
PMID:34673069
Abstract

Fluoxetine (FLX) is a psychoactive drug that acts as an antidepressant. FLX is one of the world's best-selling prescription antidepressants. FLX is widely used for the treatment of various psychiatric disorders. For these reasons, this drug may eventually end up in the aquatic environment via municipal, industrial, and hospital discharges. Even though the occurrence of FLX in aquatic environments has been reported as ubiquitous, the toxic effects that this drug may induce, especially at environmentally relevant concentrations, on essential biological processes of aquatic organisms require more attention. In the light of this information, this work aimed to investigate the influence that fluoxetine oxidative stress-induced got over the embryonic development of Danio rerio. For this purpose, D. rerio embryos (4 h post fertilization) were exposed to environmentally relevant concentrations (5, 10, 15, 20, 25, 30, 35, and 40 ng L) of fluoxetine, until 96 h post fecundation. Along the exposure, survival, alterations to embryonic development, and teratogenic effects were evaluated using a stereomicroscope. Furthermore, oxidative stress biomarkers (superoxide dismutase, catalase, glutathione peroxidase, lipid peroxidation, hydroperoxide, and carbonyl content) were evaluated at 72 and 96 h post fecundation. LC, EC, and teratogenic index were 30 ng L, 16 ng L, and 1.9, respectively. The main teratogenic effects induced by fluoxetine were pericardial edema, hatching retardation, spine alterations and craniofacial malformations. Concerning oxidative stress, our integrated biomarkers (IBR) analysis demonstrated that as the concentration increased, oxidative damage biomarkers got more influence over the embryos than antioxidant enzymes. Thus, fluoxetine induces an important oxidative stress response on the embryos of D. rerio. Collectively, our results allow us to concluded that FLX is a dangerous drug in the early life stages of D. rerio due to its high teratogenic potential and that FLX-oxidative stress induced may be involved in this toxic process.

摘要

氟西汀(FLX)是一种具有抗抑郁作用的精神活性药物。FLX 是世界上最畅销的处方抗抑郁药之一。FLX 被广泛用于治疗各种精神疾病。由于这些原因,这种药物最终可能会通过市政、工业和医院排放进入水生环境。尽管已经报道了 FLX 在水生环境中的普遍存在,但这种药物在环境相关浓度下可能对水生生物的基本生物过程产生的毒性作用,需要引起更多关注。有鉴于此,这项工作旨在研究氟西汀诱导的氧化应激对斑马鱼胚胎发育的影响。为此,将斑马鱼胚胎(受精后 4 小时)暴露于环境相关浓度(5、10、15、20、25、30、35 和 40ng/L)的氟西汀中,直到受精后 96 小时。在暴露过程中,使用立体显微镜评估存活率、胚胎发育变化和致畸作用。此外,还在受精后 72 和 96 小时评估了氧化应激生物标志物(超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、脂质过氧化、过氧化物和羰基含量)。LC、EC 和致畸指数分别为 30ng/L、16ng/L 和 1.9。氟西汀引起的主要致畸作用是心包水肿、孵化延迟、脊柱改变和颅面畸形。关于氧化应激,我们的综合生物标志物(IBR)分析表明,随着浓度的增加,氧化损伤生物标志物对胚胎的影响超过抗氧化酶。因此,氟西汀在斑马鱼胚胎中引起了重要的氧化应激反应。总的来说,我们的结果表明,由于 FLX 具有高致畸潜力,因此它在 D. rerio 的早期生命阶段是一种危险药物,并且 FLX 诱导的氧化应激可能参与了这一毒性过程。

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