Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Biomedical Sciences, Chung Shan Medical University, Taiwan.
Toxicology. 2021 Jun 30;458:152844. doi: 10.1016/j.tox.2021.152844. Epub 2021 Jun 29.
Aflatoxin B (AFB), a naturally occurring mycotoxin, is present in human placenta and cord blood. AFB at concentrations found in contaminated food commodities (0.25 and 0.5 μM) did not alter the spontaneous movement, heart rate, hatchability, or morphology of embryonic zebrafish. However, around 86 % of 0.25 μM AFB-treated embryos had livers of reduced size, and AFB disrupted the hepatocyte structures, according to histological analysis. Additionally, AFB treatment that begins at any stage before 72 h post-fertilization (hpf) effectively reduced the size of embryonic livers. In hepatic areas, AFB suppressed the expression of Hhex and Prox1, which are two critical transcriptional factors for initiating hepatoblast specification. KEGG analysis based on transcriptome profiling indicated that p53 signaling and apoptosis are the only observed pathways in AFB-treated embryos. AFB at 0.5 μM significantly activated the expression of tp53, mdm2, puma, noxa, pidd1, and gadd45aa genes that are related to the p53 pathway and also that of baxa, casp 8 and casp 3a in the apoptotic process. TUNEL staining demonstrated that AFB triggered the apoptosis of embryonic hepatocytes in a dose-dependent manner. These results indicate that the deficiency of both hhex and prox1 as well as hepatocyte apoptosis via the p53-Puma/Noxa-Bax axis may contribute to the embryonic liver shrinkage that is caused by AFB
黄曲霉毒素 B（AFB）是一种天然存在的真菌毒素，存在于人胎盘和脐血中。在受污染的食品中发现的浓度（0.25 和 0.5 μM）的 AFB 不会改变胚胎斑马鱼的自发运动、心率、孵化率或形态。然而，根据组织学分析，约 86%的 0.25 μM AFB 处理胚胎的肝脏体积减小，AFB 破坏了肝细胞结构。此外，在受精后 72 小时（hpf）之前的任何阶段开始的 AFB 处理都有效地减小了胚胎肝脏的大小。在肝区，AFB 抑制了 Hhex 和 Prox1 的表达，这两个转录因子对于启动肝母细胞特化是至关重要的。基于转录组谱分析的 KEGG 分析表明，p53 信号通路和细胞凋亡是 AFB 处理胚胎中唯一观察到的途径。0.5 μM 的 AFB 显著激活了与 p53 途径相关的 tp53、mdm2、puma、noxa、pidd1 和 gadd45aa 基因以及凋亡过程中 baxa、casp 8 和 casp 3a 的表达。TUNEL 染色表明，AFB 以剂量依赖的方式触发胚胎肝细胞凋亡。这些结果表明，hhex 和 prox1 的缺乏以及通过 p53-Puma/Noxa-Bax 轴的肝细胞凋亡可能导致 AFB 引起的胚胎肝脏缩小。
