Ivantsova Emma, Konig Isaac, Souders Christopher L, McNabney David, Simmons Denina D B, Martyniuk Christopher J
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; Department of Chemistry, Federal University of Lavras (UFLA), Minas Gerais, Brazil.
Sci Total Environ. 2023 Mar 25;866:161272. doi: 10.1016/j.scitotenv.2022.161272. Epub 2022 Dec 30.
Blood pressure medications are used to treat hypertension; however, low concentrations of beta-blockers in water systems can negatively impact aquatic wildlife. Here, we conducted a metabolic and behavioral study investigating atenolol, a beta-blocker frequently detected in global wastewater systems. The objectives were to determine the effects of low-level atenolol exposure on early stages of zebrafish. We measured survival, deformities, heartbeat, mitochondrial function, lipid and amino acid profiles, and locomotor activity to discern mechanisms of metabolic disruption. We hypothesized that atenolol disrupts lipid metabolism, which would negatively impact locomotor activity. Atenolol showed no overt toxicity to larval zebrafish up to 10 μg/L and deformities were infrequent (<5 %), and included cardiac edema and larvae with kinked tails. A hatch delay was observed at 2-day post-fertilization (dpf) for fish exposed to >5 μg/L atenolol. Heart rates were reduced in 2 and 3 dpf in fish treated with >500 ng/L atenolol. There was no change in oxygen consumption rates (basal and maximum respiration) of embryos when exposed to a range of atenolol concentrations, suggesting mitochondrial respiration was intact. Oil red staining for lipid content in larvae showed a global reduction in lipids with 10 μg/L exposure, prompting deeper investigation into the lipid profiles. Lipidomics quantified 86 lipids and revealed reduced abundance in Ceramide 18: 1 16:0 (Cer_NS d18:1_16:0), Ether linked Phosphatidylethanolamine 16:0 22:6 (EtherPE 16:0e_22:6), and Ether linked Phosphatidylcholine 16:0 22:6 (EtherPC 16:0e_22:6). We also quantified 12 amino acids and observed a subtle dose-dependent reduction in the levels of L-Histidine. Exposure to atenolol did not impact larval locomotor activity based on a Visual Motor Response test. Taken together, atenolol at environmentally relevant levels decreased heart rate of developing zebrafish and altered lipid content. As such, exposure to beta-blockers like atenolol may have negative consequences for developmental trajectories and growth of aquatic species.
血压药物用于治疗高血压；然而，水系统中低浓度的β受体阻滞剂会对水生野生动物产生负面影响。在此，我们进行了一项代谢和行为研究，调查阿替洛尔，一种在全球废水系统中经常检测到的β受体阻滞剂。目的是确定低水平阿替洛尔暴露对斑马鱼早期阶段的影响。我们测量了存活率、畸形率、心跳、线粒体功能、脂质和氨基酸谱以及运动活性，以识别代谢紊乱的机制。我们假设阿替洛尔会破坏脂质代谢，这将对运动活性产生负面影响。阿替洛尔在高达10μg/L的浓度下对斑马鱼幼体未显示明显毒性，畸形率较低（<5%），包括心脏水肿和尾巴弯曲的幼体。在受精后2天（dpf），暴露于>5μg/L阿替洛尔的鱼类出现孵化延迟。在处理>500 ng/L阿替洛尔的2和3 dpf的鱼类中，心率降低。当暴露于一系列阿替洛尔浓度时，胚胎的氧气消耗率（基础呼吸和最大呼吸）没有变化，表明线粒体呼吸完好。对幼体脂质含量进行油红染色显示，暴露于10μg/L时脂质整体减少，促使对脂质谱进行更深入的研究。脂质组学定量了86种脂质，并揭示了神经酰胺18:1 16:0（Cer_NS d18:1_16:0）、醚连接磷脂酰乙醇胺16:0 22:6（EtherPE 16:0e_22:6）和醚连接磷脂酰胆碱16:0 22:6（EtherPC 16:0e_22:6）的丰度降低。我们还定量了12种氨基酸，并观察到L-组氨酸水平有细微的剂量依赖性降低。基于视觉运动反应测试，暴露于阿替洛尔对幼体运动活性没有影响。综上所述，环境相关水平的阿替洛尔降低了发育中斑马鱼的心率并改变了脂质含量。因此，暴露于阿替洛尔等β受体阻滞剂可能对水生物种的发育轨迹和生长产生负面影响。
