2,6-二叔丁基苯酚(2,6-DTBP)已广泛用于塑料,橡胶和聚合物酚类抗氧化剂。它通过工业废物排放到水生环境中。然而,2,6-DTBP的毒性评估不足。这里,以斑马鱼胚胎为动物模型,研究2,6-DTBP的毒理学作用。结果表明,2,6-DTBP诱导线粒体功能障碍和活性氧积累,导致细胞凋亡,并进一步导致斑马鱼胚胎的发育毒性,比如延迟孵育,降低存活率,畸形率和心率增加。2,6-DTBP还可以引起斑马鱼内皮细胞(zEC)细胞核的形态学变化,抑制zEC迁移,引发异常血管生成和zEC发芽血管生成,并最终影响血管发育。此外,2,6-DTBP干扰内源性抗氧化系统,引起超氧化物歧化酶活性的变化,过氧化氢酶,和谷胱甘肽S-转移酶以及丙二醛和谷胱甘肽的含量。转录组测序显示2,6-DTBP改变了血管发育相关基因的mRNA水平,氧化应激,凋亡,细胞外基质成分和受体。综合生物标志物反应评估发现12μM2,6-DTBP具有最高的毒性。这些结果表明2,6-DTBP通过氧化应激诱导细胞凋亡,导致斑马鱼胚胎发育的毒性。这项研究有助于了解环境2,6-DTBP暴露对水生生物早期发育的影响,并提请公众注意水生生物中化学物质带来的健康风险。
2,6-di-tert-butylphenol (2,6-DTBP) has been used extensively in plastics, rubber and polymer phenolic antioxidants. It is discharged into the aquatic environment through industrial waste. However, the toxicity assessment of 2,6-DTBP is insufficient. Here, zebrafish embryos were used as an animal model to investigate the toxicological effects of 2,6-DTBP. The results showed that 2,6-DTBP induced mitochondrial dysfunction and reactive oxygen species accumulation, which caused apoptosis, and further led to developmental toxicity of zebrafish embryos, such as delayed incubation, reduced survival rate, and increased malformation rate and heart rate. 2,6-DTBP can also cause morphological changes in the zebrafish endothelial cell (zEC) nucleus, inhibit zEC migration, trigger abnormal angiogenesis and zEC sprouting angiogenesis, and ultimately affect vascular development. In addition, 2,6-DTBP interfered with the endogenous antioxidant system, causing changes in activities of superoxide dismutase, catalase, and glutathione S-transferase and contents of malondialdehyde and glutathione. Transcriptome sequencing showed that 2,6-DTBP altered the mRNA levels of genes associated with vascular development, oxidative stress, apoptosis, extracellular matrix components and receptors. Integrative biomarker response assessment found that 12 μM 2,6-DTBP had the highest toxicity. These results indicated that 2,6-DTBP induced apoptosis through oxidative stress, leading to toxicity of zebrafish embryo development. This study contributes to understanding the effects of environmental 2,6-DTBP exposure on early development of aquatic organisms and draws public attention to the health risks posed by chemicals in aquatic organisms.