Chrysene, a four-ring polycyclic aromatic hydrocarbon, induces hepatotoxicity in mice by activation of the aryl hydrocarbon receptor (AhR)
Chrysene, a four-ring polycyclic aromatic hydrocarbon, induces hepatotoxicity in mice by activation of the aryl hydrocarbon receptor (AhR)
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Chrysene 是一种四环多环芳香烃，通过激活芳烃受体 (AhR) 诱导小鼠肝毒性。
DOI：
10.1016/j.chemosphere.2021.130108
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发表时间：
2021-03-09
期刊：
影响因子：
8.8
通讯作者：
Zhang, Shu-Yun
中科院分区：
文献类型：
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作者：
Tao, Li-Ping;Li, Xue;Zhang, Shu-Yun
多环芳烃（PAHs）是一组持久性有机污染物，对人类健康造成严重危害。在这里，我们评估了金，这是一个四环多环芳烃和16个优先多环芳烃的重要成员，对肝脏的不良影响。在一些常见的生、熟中国食物样本中检测到了金黄色葡萄球菌。在暴露于屈的C57 BL/6小鼠中观察到肝毒性，包括相对肝脏重量增加、肝细胞肿胀和变性以及血清丙氨酸氨基转移酶（ALT）水平升高。谷氨酰胺治疗可通过降低血清ALT水平有效地改善小鼠的肝损伤。克雷伯胺诱导小鼠肝脏谷胱甘肽耗竭和氧化性DNA损伤，并增加8-羟基-2'-脱氧鸟苷（8-OHdG）水平。结果表明，染毒C57 BL/6小鼠肝脏中芳烃受体（AhR）、AhR相关靶基因（包括CYP1A1、CYP1A2和CYP1B1）和AhR核转位蛋白（ARNT）的表达水平显著升高。克雷伯氏菌诱导的小鼠肝脏核因子红细胞2相关因子2（Nrf2）和Nrf2介导的II期解毒和抗氧化酶（包括NQO 1、UGT 1A1、UGT 1A6、SULT 1A1、GSTm1、GSTm3、过氧化氢酶（CAT）、GPx 1和SOD 2）的mRNA水平。结果表明，黄曲霉毒素对AhR（+/+）小鼠有明显的毒性作用，包括肝重增加和血清ALT水平升高，但对AhR（-/-）小鼠无明显毒性作用。在AhR（+/+）小鼠中，克雷伯汀显著诱导肝脏CYP1A1和CYP1A2 mRNA水平，但对AhR（-/-）小鼠无显著影响。据我们所知，本研究首次证明了由金黄色葡萄球菌引起的肝毒性依赖于AhR，而Nrf2在金黄色葡萄球菌诱导的氧化性肝损伤保护中起着重要的调节作用。(C)2021爱思唯尔有限公司版权所有。
Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic global environmental pollutants and cause harmful effects on human health. Here, we evaluated adverse effects of chrysene, which is a four-ring PAH and an important member of 16 priority PAHs, on the liver. Chrysene was detected in some common raw and cooked Chinese food samples. Hepatotoxicity including increased relative liver weight, hepatocyte swelling and degeneration, and elevated serum alanine aminotransferase (ALT) levels were observed in chrysene-exposed C57BL/6 mice. Glutamine treatment effectively ameliorated chrysene-induced mice liver injury by decreasing serum ALT levels. Chrysene induced mice hepatic glutathione depletion and oxidative DNA damage with increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Hepatic expression levels of the aryl hydrocarbon receptor (AhR), AhR-related target genes including CYP1A1, CYP1A2 and CYP1B1, and AhR nuclear translocator (ARNT) were significantly increased in chrysene-exposed C57BL/6 mice. Chrysene induced mice hepatic mRNA levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated phase II detoxifying and antioxidant enzymes including NQO1, UGT1A1, UGT1A6, SULT1A1, GSTm1, GSTm3, Catalase (CAT), GPx1, and SOD2. We found that chrysene had toxic effects including increased relative liver weight and elevated serum ALT levels on AhR(+/+) mice but not AhR(-/-) mice. Chrysene significantly induced hepatic mRNA levels of CYP1A1 and CYP1A2 in AhR(+/+) mice but not AhR(-/-) mice. To our knowledge, this study is the first to demonstrate that hepatotoxicity causes by chrysene is dependent on AhR, and Nrf2 plays an important regulation role in protection against oxidative liver injury induced by chrysene. (C) 2021 Elsevier Ltd. All rights reserved.