Physiological and transcriptomic changes of zebrafish (Danio rerio) in response to Isopropylate Triphenyl Phosphate (IPPP) exposure

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2024-08-08 DOI:10.1016/j.etap.2024.104528

Qiong Zhang , Shukai Zheng , Xiaoling Shi , Congying Luo , Wenlong Huang , Yanhong Huang , Wenying Wu , Kusheng Wu

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引用次数: 0

Abstract

Isopropylate Triphenyl Phosphate (IPPP), a novel organophosphorus flame retardant, has become a widespread environmental pollutant. However, the toxic effects and mechanisms of IPPP remain unclear. In this study, we evaluated the neurodevelopmental toxicity effects of IPPP on zebrafish embryonic development, neurobehavior, and physiological and transcriptomic changes. The results showed that IPPP induced adverse developments such as low survival rates and hatching rates, decreased body length and eye distance, and also led to increased heart rates and embryonic malformation rates. The developmental defects mainly included typical pericardial edema, eye deformities, and a reduction in the number of newborn neurons. Mitochondrial energy metabolism disorders and apoptosis of cardiomyocytes may be responsible for heart malformation. Behavioral results showed that IPPP caused abnormal changes in swimming speed, total swimming distance and trajectory, and showed a low-dose effect. In addition, the decreased activity of neurotransmitters such as acetylcholinesterase (AchE) and dopamine (DA), and the changes in genes related to the central nervous system (CNS) and metabolism pathway may be the causes of neurodevelopmental toxicity of IPPP. Meanwhile, IPPP induced oxidative stress and apoptosis, and changed the ATPase activity of zebrafish larvae by altering nuclear factor erythroid2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing results indicated that Cytochrome P450 and drug metabolism, Energy metabolism-related pathways, Glutathione metabolism, Retinoid acid (RA) and REDOX signaling pathways were significantly enriched, and most of the genes in these pathways were up-regulated after IPPP treatment, which may be new targets for IPPP-induced neurodevelopment. In summary, the results of this study provide an important reference for a comprehensive assessment of the toxic effects and health risks of the new pollutant IPPP.

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斑马鱼（Danio rerio）暴露于磷酸三苯酯异丙酯（IPPP）后的生理变化和转录组变化

三苯基磷酸异丙酯（IPPP）是一种新型有机磷阻燃剂，已成为一种广泛存在的环境污染物。然而，IPPP 的毒性作用和机制仍不清楚。本研究评估了 IPPP 对斑马鱼胚胎发育、神经行为、生理和转录组变化的神经发育毒性效应。结果表明，IPPP诱导了斑马鱼的不良发育，如低存活率和孵化率、体长和眼距下降，还导致心率和胚胎畸形率上升。发育缺陷主要包括典型的心包水肿、眼睛畸形和新生神经元数量减少。线粒体能量代谢紊乱和心肌细胞凋亡可能是导致心脏畸形的原因。行为学结果表明，IPPP 会导致游泳速度、总游泳距离和轨迹发生异常变化，并表现出低剂量效应。此外，乙酰胆碱酯酶（AchE）和多巴胺（DA）等神经递质的活性降低，以及中枢神经系统（CNS）和代谢途径相关基因的变化，可能是 IPPP 神经发育毒性的原因。同时，IPPP通过改变核因子红细胞相关因子2（Nrf2）和线粒体信号通路，分别诱导氧化应激和细胞凋亡，并改变斑马鱼幼体的ATP酶活性。转录组测序结果表明，细胞色素P450和药物代谢、能量代谢相关通路、谷胱甘肽代谢、维甲酸（RA）和REDOX信号通路显著富集，这些通路中的大部分基因在IPPP处理后上调，可能是IPPP诱导神经发育的新靶点。总之，本研究结果为全面评估新型污染物 IPPP 的毒性效应和健康风险提供了重要参考。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.