School of Environmental and Chemical Engineering, Shanghai University, Shanghai, China.
Environ Toxicol Chem. 2013 Aug;32(8):1793-9. doi: 10.1002/etc.2245. Epub 2013 Jun 13.
Bisphenol A (BPA) and nonylphenol (NP) are well known endocrine-disrupting chemicals (EDCs) ubiquitous in the aquatic environment and are an ecotoxicological risk for the health of aquatic organisms. Limited attention has been given to the immunotoxicity of these chemicals. The present study revealed a concentration-dependent increase of reactive oxygen species content and an induced expression of redox-sensitive transcription factors in zebrafish embryos after exposure to various concentrations of BPA, NP, and BPA/NP mixture for 4 h to 168 h postfertilization. Transcription of genes related to the immune response, including IFNγ, IL1β, IL10, Mx, TNFα, CC-chemokine, and CXCL-clc, were significantly up-regulated on exposure to EDCs. A significant induction of concentrations of proinflammatory mediator, nitric oxide, accompanied by an increase in the activity of nitric oxide synthase (NOS) and an upregulation of inducible NOS gene expression, was detected in zebrafish embryos on exposures to EDCs. To elucidate the potential mechanisms by which BPA and NP activate the innate immune response, expression profiles of genes related to the Toll-like receptors (TLRs) signaling pathway were examined. Expressions of TLR3, TRIF, MyD88, SARM, IRAK4, and TRAF6 were altered on exposure to EDCs. The authors' results demonstrate that exposure to BPA and NP significantly affects the expression of genes related to immune response in zebrafish embryos following oxidative stress.
双酚 A(BPA)和壬基酚(NP)是众所周知的内分泌干扰化学物质(EDCs),广泛存在于水生环境中,对水生生物的健康构成生态毒理学风险。这些化学物质的免疫毒性受到的关注有限。本研究表明,在受精后 4 小时至 168 小时内,暴露于不同浓度的 BPA、NP 和 BPA/NP 混合物中,斑马鱼胚胎的活性氧物质含量和氧化还原敏感转录因子的表达呈浓度依赖性增加。在接触 EDCs 后,与免疫反应相关的基因,包括 IFNγ、IL1β、IL10、Mx、TNFα、CC-趋化因子和 CXCL-clc 的转录显著上调。在接触 EDCs 后,检测到斑马鱼胚胎中促炎介质一氧化氮的浓度显著诱导,伴随着一氧化氮合酶(NOS)活性的增加和诱导型 NOS 基因表达的上调。为了阐明 BPA 和 NP 激活先天免疫反应的潜在机制,研究了与 Toll 样受体(TLRs)信号通路相关的基因表达谱。TLR3、TRIF、MyD88、SARM、IRAK4 和 TRAF6 的表达在接触 EDCs 后发生改变。作者的研究结果表明,暴露于 BPA 和 NP 会显著影响斑马鱼胚胎中与免疫反应相关的基因表达,引发氧化应激。