In vivo assessment of respiratory burst inhibition by xenobiotic exposure using larval zebrafish

Currently assessment of the potential immunotoxicity of a given agent involves a tiered approach for hazard identification and mechanistic studies, including observational studies, evaluation of immune function, and measurement of susceptibility to infectious and neoplastic diseases. These studies generally use costly low-throughput mammalian models. Zebrafish, however, offer an excellent alternative due to their rapid development, ease of maintenance, and homology to mammalian immune system function and development. Larval zebrafish also are a convenient model to study the innate immune system with no interference from the adaptive immune system. In this study, a respiratory burst assay (RBA) was utilized to measure reactive oxygen species (ROS) production after developmental xenobiotic exposure. Embryos were exposed to non-teratogenic doses of chemicals and at 96 hr post-fertilization, the ability to produce ROS was measured. Using the RBA, 12 compounds with varying immune-suppressive...

当前，对特定物质潜在免疫毒性的评估采用分级评估法开展危害识别与机制研究，涵盖观察性研究、免疫功能评估以及对感染性与肿瘤性疾病易感性的检测。此类研究通常需使用成本高昂、通量较低的哺乳动物模型。然而，斑马鱼（Zebrafish）是极佳的替代模型：其发育迅速、饲养便捷，且免疫系统的功能与发育过程与哺乳动物具有高度同源性。幼龄斑马鱼亦是研究先天免疫系统的便捷模型，不会受到适应性免疫系统的干扰。本研究采用呼吸爆发试验（respiratory burst assay, RBA），以检测发育阶段暴露于外源性物质后活性氧（reactive oxygen species, ROS）的生成水平。研究人员将斑马鱼胚胎暴露于非致畸剂量的化学物质中，并在受精后96小时检测其产生活性氧的能力。通过该试验，本研究共筛选出12种具有不同免疫抑制活性的化合物……