Department of Plastic Surgery and Burns Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China; Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong 515041, China; Shantou Plastic surgery Clinical Research Center, Shantou, Guangdong 515041, China.
Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong 515041, China.
Ecotoxicol Environ Saf. 2023 Nov 15;267:115615. doi: 10.1016/j.ecoenv.2023.115615. Epub 2023 Oct 25.
Polybrominated diphenyl ether flame retardants are known to have adverse effects on the development of organisms. We investigated the molecular mechanisms associated with the developmental hazards of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in zebrafish, as well as the behavioral and morphological alterations involved, focusing on endoplasmic reticulum stress (ERS), oxidative stress, and apoptosis. Our study revealed behavioral alterations in zebrafish exposed to BDE-47, including impaired motor activity, reduced exploration, and abnormal swimming patterns. In addition, we observed malformations in craniofacial regions and other developmental abnormalities that may be associated with ERS-induced cellular dysfunction. BDE-47 exposure showed apparent changes in ERS, oxidative stress, and apoptosis biomarkers at different developmental stages in zebrafish through gene expression analysis and enzyme activity assays. The study indicated that exposure to BDE-47 results in ERS, as supported by the upregulation of ERS-related genes and increased activity of ERS markers. In addition, oxidative stress-related genes showed different expression patterns, suggesting that oxidative stress is involved in the BDE-47 toxic effects. Moreover, an assessment of apoptotic biomarkers revealed an imbalance in the expression levels of pro- and anti-apoptotic genes, suggesting that BDE-47 exposure activated the apoptotic pathway. These results highlight the complex interactions between ERS, oxidative stress, apoptosis, behavioral alterations, and morphological malformations following BDE-47 exposure in zebrafish. Understanding the mechanisms of toxicity of developmental hazards is essential to elucidate the toxicological effects of environmental contaminants. The knowledge can help develop strategies to mitigate their adverse effects on the health of ecosystems and humans.
多溴联苯醚阻燃剂已被证实对生物体的发育具有不良影响。我们研究了 2,2',4,4'-四溴二苯醚（BDE-47）在斑马鱼发育危害相关的分子机制，以及涉及的行为和形态改变，重点关注内质网应激（ERS）、氧化应激和细胞凋亡。我们的研究揭示了 BDE-47 暴露的斑马鱼的行为改变，包括运动活动受损、探索减少和异常游泳模式。此外，我们观察到颅面区域和其他发育异常的畸形，这可能与 ERS 诱导的细胞功能障碍有关。通过基因表达分析和酶活性测定，我们发现 BDE-47 暴露在不同发育阶段的斑马鱼中，ERS、氧化应激和细胞凋亡生物标志物明显改变。该研究表明，暴露于 BDE-47 会导致 ERS，这得到了 ERS 相关基因上调和 ERS 标志物活性增加的支持。此外，氧化应激相关基因表现出不同的表达模式，表明氧化应激参与了 BDE-47 的毒性作用。此外，对凋亡生物标志物的评估显示，促凋亡和抗凋亡基因的表达水平失衡，表明 BDE-47 暴露激活了凋亡途径。这些结果强调了 ERS、氧化应激、细胞凋亡、行为改变和形态畸形之间的复杂相互作用，以及 BDE-47 暴露对斑马鱼的影响。了解发育危害毒性的机制对于阐明环境污染物的毒理学效应至关重要。这些知识可以帮助制定策略来减轻它们对生态系统和人类健康的不利影响。
