Centre for Environmental and Marine Studies (CESAM), Department of Biology, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
Department of Analytical Chemistry and Applied (Chromatography Section), School of Engineering, Institut Químic de Sarrià-Universitat Ramon Llull, Via Augusta 390, 08017, Barcelona, Spain.
Chemosphere. 2023 Dec;345:140468. doi: 10.1016/j.chemosphere.2023.140468. Epub 2023 Oct 16.
Fluoxetine is widely prescribed for the treatment of depressive states, acting at the level of the central nervous system, consequently affecting non-target organisms. This study aimed to investigate the influence of environmentally relevant fluoxetine concentrations (1-1000 ng/L) on Danio rerio development, assessing both embryotoxicity and behavior, antioxidant defense, gene expression and neurotransmitter levels at larval stage. Exposure to fluoxetine during early development was found to be able to accelerate embryo hatching in embryos exposed to 1, 10 and 100 ng/L, reduce larval size in 1000 ng/L, and increase heart rate in 10, 100 and 1000 ng/L exposed larvae. Behavioral impairments (decreased startle response and increased larvae locomotor activity) were associated with effects on monoaminergic systems, detected through the downregulation of key genes (vmat2, mao, tph1a and th2). In addition, altered levels of neurochemicals belonging to the serotonergic and dopaminergic systems (increased levels of tryptophan and norepinephrine) highlighted the sensitivity of early life stages of zebrafish to low concentrations of fluoxetine, inducing effects that may compromise larval survival. The obtained data support the necessity to test low concentrations of SSRIs in environmental risk assessment and the use of biomarkers at different levels of biological organization for a better understanding of modes of action.
氟西汀被广泛用于治疗抑郁状态，作用于中枢神经系统水平，从而影响非靶标生物。本研究旨在调查环境相关浓度的氟西汀（1-1000ng/L）对斑马鱼发育的影响，评估胚胎毒性和行为、抗氧化防御、幼虫阶段的基因表达和神经递质水平。研究发现，早期胚胎暴露于氟西汀会加速 1、10 和 100ng/L 暴露胚胎的孵化，减少 1000ng/L 暴露幼虫的体型，增加 10、100 和 1000ng/L 暴露幼虫的心率。行为损伤（惊跳反应降低和幼虫运动活性增加）与单胺能系统的影响相关，这是通过关键基因（vmat2、mao、tph1a 和 th2）的下调检测到的。此外，属于 5-羟色胺能和多巴胺能系统的神经化学物质水平的改变（色氨酸和去甲肾上腺素水平升高）突出了斑马鱼早期生活阶段对低浓度氟西汀的敏感性，诱导可能危及幼虫生存的影响。所获得的数据支持在环境风险评估中测试 SSRIs 低浓度的必要性，并在不同的生物组织水平使用生物标志物，以更好地了解作用模式。
