Cardiac toxicity of 5-ring polycyclic aromatic hydrocarbons is differentially dependent on the aryl hydrocarbon receptor 2 isoform during zebrafish development
Cardiac toxicity of 5-ring polycyclic aromatic hydrocarbons is differentially dependent on the aryl hydrocarbon receptor 2 isoform during zebrafish development
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DOI：
10.1016/j.taap.2011.09.010
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发表时间：
2011-12-01
影响因子：
3.8
通讯作者：
Scholz, Nathaniel L.
中科院分区：
文献类型：
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作者：
Incardona, John P.;Linbo, Tiffany L.;Scholz, Nathaniel L.
石油衍生化合物，包括多环芳烃（PAH），通常以复杂的混合物存在于环境中。最近使用斑马鱼实验模型的研究表明，多环芳烃对胚胎心血管系统具有毒性，并且这种发育心脏毒性的严重程度和性质因个体多环芳烃而异。在本研究中，我们表征了相对较高分子量的5-环多环芳烃苯并[a]芘（BaP），苯并[e]芘（BeP），苯并[k]荧蒽（BkF）的毒性。虽然所有三种化合物都靶向心血管系统，但配体激活的芳烃受体（AHR 2）的潜在作用和细胞色素p450代谢途径（CYP 1A）的组织特异性诱导作用各不相同。BaP暴露（401 μ M）产生AHR 2依赖性心动过缓，心包水肿和心肌CYP 1A免疫荧光。相比之下，BkF暴露（4-40 μ M）引起更严重的心包水肿、成环缺陷和通过房室瓣的红细胞反流，这些都是AHR 2非依赖性的（即，缺乏心肌或内皮细胞CYP 1A诱导）。最后，暴露于BeP（401 μ M）产生了低水平的CYP 1A+信号的血管内皮细胞的头部和躯干，没有明显的毒性作用，对心脏功能或形态发生。结合早期对3环和4环多环芳烃的研究，我们的研究结果提供了一个更完整的图片，说明单个多环芳烃如何驱动它们占主导地位的混合物的心脏毒性。这将改善对野生鱼类种群的毒性伤害评估和风险评估，这些鱼类种群在因石油泄漏、城市雨水径流或遗留工业活动污染的沉积物等与石油有关的人类影响重叠而改变的生境中产卵。爱思唯尔公司出版
Petroleum-derived compounds, including polycyclic aromatic hydrocarbons (PAHs), commonly occur as complex mixtures in the environment. Recent studies using the zebrafish experimental model have shown that PAHs are toxic to the embryonic cardiovascular system, and that the severity and nature of this developmental cardiotoxicity varies by individual PAH. In the present study we characterize the toxicity of the relatively higher molecular weight 5-ring PAHs benzo[a]pyrene (BaP), benzo[e]pyrene (BeP), and benzo[k]fluoranthene (BkF). While all three compounds target the cardiovascular system, the underlying role of the ligand-activated aryl hydrocarbon receptor (AHR2) and the tissue-specific induction of the cytochrome p450 metabolic pathway (CYP1A) were distinct for each. BaP exposure (401 mu M) produced AHR2-dependent bradycardia, pericardial edema, and myocardial CYP1A immunofluorescence. By contrast, BkF exposure (4-40 mu M) caused more severe pericardial edema, looping defects, and erythrocyte regurgitation through the atrioventricular valve that were AHR2-independent (i.e., absent myocardial or endocardial CYP1A induction). Lastly, exposure to BeP (401 mu M) yielded a low level of CYP1A+ signal in the vascular endothelium of the head and trunk, without evident toxic effects on cardiac function or morphogenesis. Combined with earlier work on 3- and 4-ring PAHs, our findings provide a more complete picture of how individual PAHs may drive the cardiotoxicity of mixtures in which they predominate. This will improve toxic injury assessments and risk assessments for wild fish populations that spawn in habitats altered by overlapping petroleum-related human impacts such as oil spills, urban stormwater runoff, or sediments contaminated by legacy industrial activities. Published by Elsevier Inc.