State Key Laboratory of Tea Plant Biology and Utilization, Key Lab of Food Nutrition and Safety, School of Tea and Food Science & Technology, Anhui Agricultural University, Hefei, 230036, China; Institute of Quality Standards & Testing Technology for Agro-Products, Key Laboratory of Agro-product Quality and Safety, Chinese Academy of Agricultural Sciences, Key Laboratory of Agri-food Quality and Safety, Ministry of Agriculture and Rural Affairs, Beijing, 100081, China.
Institute of Quality Standards & Testing Technology for Agro-Products, Key Laboratory of Agro-product Quality and Safety, Chinese Academy of Agricultural Sciences, Key Laboratory of Agri-food Quality and Safety, Ministry of Agriculture and Rural Affairs, Beijing, 100081, China.
Ecotoxicol Environ Saf. 2020 May;194:110338. doi: 10.1016/j.ecoenv.2020.110338. Epub 2020 Mar 2.
2,2',3,5',6-Pentachlorobiphenyl (PCB95) is known as a persistent pollutant that was found in eggs in China. PCB 95 can be metabolized into OH-PCB95 and MeO-PCB95 in liver microsomes. However, the toxicity and its mechanism of PCB95 or its metabolites have been little studied on laying hens. Herein, chicken embryo liver cells of laying hens were selected and treated with different levels of PCB95 and its two metabolites, and the EC of PCB95, OH-PCB95, MeO-PCB95 was 80.85, 4.81 and 107.04 μg/mL respectively, indicating that OH-PCB95 is much more cytotoxic than PCB95 or MeO-PCB95. Targeted metabolomics was further used to study the effects of the parent compound and its metabolites on cell metabolism. The results showed that four primary types of glycerophospholipids were down-regulated after exposure to PCB95 and its metabolites, especially PE and PS (60% more than the control for PCB95, 40% for OH-PCB95, and less than 40% for MeO-PCB95). KEGG pathway analysis based on amino acid metabolism showed that PCB95 may mainly interfere with the amino acids involved in immune regulation (phenylalanine and tyrosine), and OH-PCB95 may be associated with genetic disoders (cysteine, methionine and purine metabolism). However, the metabolic pathways induced by MeO-PCB95 are quite different from those induced by PCB95 and OH-PCB95, affecting mainly D-glutamine and D-glutamate metabolism, alanine and glutamate metabolism, and arginine and proline metabolism; these pathways mainly regulate the elimination of excess purines and are involved in the synthesis of the amino acids required by cells. These results showed that OH-PCB95 has the highest toxicity on chicken embryo liver cells and MeO-PCB95 could be a detoxification product of PCB95 and OH-PCB95. This study contributes to the understanding of the different effects of PCB95 and its metabolites on cellular metabolism, and the data are helpful in evaluating the hepatotoxic effects of these compounds.
2,2',3,5',6-五氯联苯（PCB95）是一种持久性污染物，在中国的鸡蛋中被发现。PCB95 在肝微粒体中可以代谢为 OH-PCB95 和 MeO-PCB95。然而，PCB95 或其代谢物的毒性及其机制在产蛋鸡中研究甚少。在此，选择鸡胚肝细胞进行不同水平的 PCB95 及其两种代谢物的处理，结果显示 PCB95、OH-PCB95 和 MeO-PCB95 的 EC50 值分别为 80.85、4.81 和 107.04μg/mL，表明 OH-PCB95 的细胞毒性比 PCB95 或 MeO-PCB95 高得多。进一步采用靶向代谢组学研究了母体化合物及其代谢物对细胞代谢的影响。结果表明，暴露于 PCB95 及其代谢物后，四种主要类型的甘油磷脂下调，特别是 PE 和 PS（与对照组相比，PCB95 上调 60%，OH-PCB95 上调 40%，MeO-PCB95 上调不到 40%）。基于氨基酸代谢的 KEGG 途径分析表明，PCB95 可能主要干扰参与免疫调节的氨基酸（苯丙氨酸和酪氨酸），而 OH-PCB95 可能与遗传疾病有关（半胱氨酸、蛋氨酸和嘌呤代谢）。然而，MeO-PCB95 诱导的代谢途径与 PCB95 和 OH-PCB95 诱导的代谢途径大不相同，主要影响 D-谷氨酰胺和 D-谷氨酸代谢、丙氨酸和谷氨酸代谢以及精氨酸和脯氨酸代谢；这些途径主要调节多余嘌呤的消除，参与细胞所需氨基酸的合成。这些结果表明，OH-PCB95 对鸡胚肝细胞的毒性最高，而 MeO-PCB95 可能是 PCB95 和 OH-PCB95 的解毒产物。本研究有助于了解 PCB95 及其代谢物对细胞代谢的不同影响，为评价这些化合物的肝毒性提供了数据支持。
