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.
Comp Biochem Physiol C Toxicol Pharmacol. 2022 Mar;253:109265. doi: 10.1016/j.cbpc.2021.109265. Epub 2022 Jan 3.
Phenytoin (PHE) is an antiepileptic drug that has been widely used in clinical practice for about 80 years. It is mainly used in the treatment of tonic-clonic and partial seizures. The widespread consumption of this drug around the world has led to PHE being introduced into water bodies through municipal, hospital, and industrial effluent discharges. Since the toxic effects of this drug on aquatic species has been scarcely explored, the aim of this work was to investigate the influence of low (25-400 ngL) and high (500-1500 ngL) environmentally relevant concentrations of PHE on the development and oxidative status of zebrafish (Danio rerio) embryos. The toxicity of PHE was evaluated from 12 to 96 h after fertilization in D. rerio at concentrations between 25 and 1500 ngL. In both the control group and the 0.05% DMSO system, no malformations were observed, all embryos developed normally after 96 h. The severity and frequency of malformations increased with increasing PHE concentration compared to embryos in the control group. Malformations observed included developmental delay, hypopigmentation, miscellaneous (more than one malformation in the same embryo), modified chorda structure, tail malformation, and yolk deformation. Concerning the biomarkers of oxidative stress, an increase in the degree of lipid peroxidation, protein carbonylation, and hydroperoxide content was observed (p < 0.05) concerning the control. In addition, a significant increase (p < 0.05) in antioxidant enzymes (SOD, CAT, and GPx) was observed at low exposure concentrations (25-400 ngL), with a decrease in enzyme activity at high concentrations (500-1500 ngL). Our IBR analysis demonstrated that oxidative damage biomarkers got more influence at 500ngL of PHE. The results demonstrated that PHE may affect the embryonic development of zebrafish and that oxidative stress may be involved in the generation of this embryotoxic process.
苯妥英（PHE）是一种抗癫痫药物，已在临床实践中使用了大约 80 年。它主要用于治疗强直阵挛和部分发作。这种药物在全世界的广泛使用导致其通过城市、医院和工业废水排放进入水体。由于这种药物对水生物种的毒性作用尚未得到充分探索，因此本工作的目的是研究低（25-400ngL）和高（500-1500ngL）环境相关浓度的 PHE 对斑马鱼（Danio rerio）胚胎发育和氧化状态的影响。在 25 至 1500ngL 浓度下，在受精后 12 至 96 小时评估 PHE 在 D. rerio 中的毒性。在对照组和 0.05%DMSO 系统中，均未观察到畸形，所有胚胎在 96 小时后均正常发育。与对照组相比，随着 PHE 浓度的增加，畸形的严重程度和频率增加。观察到的畸形包括发育迟缓、色素减退、混杂（同一胚胎中出现多种畸形）、改变的脊索结构、尾巴畸形和卵黄变形。关于氧化应激生物标志物，与对照组相比，观察到脂质过氧化、蛋白质羰基化和过氧化物含量增加（p<0.05）。此外，在低暴露浓度（25-400ngL）下，抗氧化酶（SOD、CAT 和 GPx）的活性显著增加（p<0.05），而在高浓度（500-1500ngL）下，酶活性下降。我们的 IBR 分析表明，在 500ngL 的 PHE 下，氧化损伤生物标志物的影响更大。结果表明，PHE 可能影响斑马鱼的胚胎发育，氧化应激可能参与了这种胚胎毒性过程的产生。
