Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611, USA.
Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611, USA.
Environ Pollut. 2024 Nov 15;361:124767. doi: 10.1016/j.envpol.2024.124767. Epub 2024 Aug 20.
Citalopram is a selective serotonin reuptake inhibitor (SSRI) used to treat depression and is often detected in aquatic environments. Here, we measured the acute toxicity of citalopram at environmentally relevant concentrations to zebrafish embryos/larvae and utilized RNA-seq to reveal potential mechanisms of toxicity. We also assessed behavioral outcomes in larval zebrafish. Zebrafish embryos were exposed continuously to embryo rearing medium (ERM), or one concentration of 0.1, 1, 10, 100, and 1000 μg/L citalopram for 7 days post-fertilization (dpf). No acute toxicity was noted for citalopram over 7-days in developing zebrafish, nor were there any effects on hatch rates; however, exposure resulted in a dose-dependent decrease in heart rate at 2 dpf. Reactive oxygen species were also increased in 7-day old larvae zebrafish exposed to 100 μg/L citalopram. There were 29 genes differentially expressed in fish exposed to 10 μg/L citalopram [FDR <0.05] and 79 genes differentially expressed in fish exposed to 1000 μg/L citalopram [FDR <0.05]. In the 1000 μg/L citalopram treatment, there were several transcripts downregulated related to muscle function, including myhz2, myhz1, and myom1. Twenty-five gene set pathways were shared between exposure concentrations including 'IL6 Expression Targets', 'Thyroid Stimulating Hormone (TSH) Resistance in Congenital Hypothyroidism', and 'GFs/TNF - > Ion Channels.' Enrichment of KEGG pathways revealed that 1000 μg/L citalopram altered processes related to the proteosome and cardiac muscle contractions. Larval zebrafish at 7 dpf showed hypoactivity with exposure to ≥10 μg/L citalopram. This may be related to the downregulation of transcripts involved in muscle function. Overall, our results show that citalopram as a pharmaceutical pollutant may have an adverse influence on aquatic species' ability to survive by reducing their abilities to elude predators (e.g. cardiac output, locomotor activity). This study improves mechanistic understanding of the potential harm citalopram may cause fish and contributes to environmental risk assessments for SSRIs in aquatic species.
西酞普兰是一种选择性 5-羟色胺再摄取抑制剂（SSRI），用于治疗抑郁症，经常在水生环境中检测到。在这里，我们测量了西酞普兰在环境相关浓度下对斑马鱼胚胎/幼虫的急性毒性，并利用 RNA 测序揭示了潜在的毒性机制。我们还评估了幼鱼的行为结果。斑马鱼胚胎在受精后 7 天（dpf）持续暴露于胚胎饲养培养基（ERM）或 0.1、1、10、100 和 1000μg/L 西酞普兰的一种浓度下。在发育中的斑马鱼中，7 天内西酞普兰没有表现出急性毒性，孵化率也没有受到影响；然而，暴露导致 2 dpf 时心率呈剂量依赖性下降。在暴露于 100μg/L 西酞普兰的 7 天大的幼鱼中，活性氧也增加了。在暴露于 10μg/L 西酞普兰的鱼中，有 29 个基因差异表达 [FDR<0.05]，在暴露于 1000μg/L 西酞普兰的鱼中有 79 个基因差异表达 [FDR<0.05]。在 1000μg/L 西酞普兰处理中，有几个与肌肉功能相关的转录物下调，包括 myhz2、myhz1 和 myom1。在暴露浓度之间有 25 个基因集途径共享，包括“IL6 Expression Targets”、“先天性甲状腺功能减退症中的甲状腺刺激激素（TSH）抵抗”和“GFs/TNF->离子通道”。KEGG 途径的富集表明，1000μg/L 西酞普兰改变了与蛋白酶体和心肌收缩相关的过程。在 7 dpf 的幼鱼中，暴露于≥10μg/L 西酞普兰时表现出活动减少。这可能与涉及肌肉功能的转录物下调有关。总的来说，我们的结果表明，作为一种药物污染物，西酞普兰可能通过降低逃避捕食者的能力（例如心输出量、运动活性）对水生物种的生存能力产生不利影响。这项研究提高了对西酞普兰可能对鱼类造成的潜在危害的机制理解，并为水生物种中 SSRIs 的环境风险评估做出了贡献。
