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.

多环芳烃（PAHs）是一组持久性有机全球环境污染物，对人类健康造成有害影响。在这里，我们评估了 chrysene 对肝脏的不利影响，chrysene 是一种四环 PAH，是 16 种优先 PAH 的重要成员。在一些常见的生熟中餐样本中检测到了 Chrysene。在暴露于 chrysene 的 C57BL/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。谷氨酰胺治疗通过降低血清 ALT 水平有效改善了 chrysene 诱导的小鼠肝损伤。Chrysene 诱导小鼠肝谷胱甘肽耗竭和氧化性 DNA 损伤，增加 8-羟基-2'-脱氧鸟苷 (8-OHdG) 水平。在暴露于 chrysene 的 C57BL/6 小鼠中，芳烃受体 (AhR)、AhR 相关靶基因（包括 CYP1A1、CYP1A2 和 CYP1B1）和 AhR 核转运蛋白 (ARNT) 的肝表达水平显着增加。Chrysene 诱导小鼠肝脏 mRNA 水平的核因子红细胞 2 相关因子 2 (Nrf2) 和 Nrf2 介导的 II 期解毒和抗氧化酶包括 NQO1、UGT1A1、UGT1A6、SULT1A1、GSTm1、GSTm3、过氧化氢酶 (CAT)、GPx1 和SOD2。我们发现 chrysene 具有毒性作用，包括增加相对肝脏重量和升高的血清 ALT 水平对 AhR Chrysene 诱导小鼠肝脏 mRNA 水平的核因子红细胞 2 相关因子 2 (Nrf2) 和 Nrf2 介导的 II 期解毒和抗氧化酶包括 NQO1、UGT1A1、UGT1A6、SULT1A1、GSTm1、GSTm3、过氧化氢酶 (CAT)、GPx1 和SOD2。我们发现 chrysene 具有毒性作用，包括增加相对肝脏重量和升高的血清 ALT 水平对 AhR Chrysene 诱导小鼠肝脏 mRNA 水平的核因子红细胞 2 相关因子 2 (Nrf2) 和 Nrf2 介导的 II 期解毒和抗氧化酶包括 NQO1、UGT1A1、UGT1A6、SULT1A1、GSTm1、GSTm3、过氧化氢酶 (CAT)、GPx1 和SOD2。我们发现 chrysene 具有毒性作用，包括增加相对肝脏重量和升高的血清 ALT 水平对 AhR^+/+小鼠，但不是 AhR ^-/-小鼠。^{Chrysene 在 AhR +/+}小鼠中显着诱导肝脏 CYP1A1 和 CYP1A2 的 mRNA 水平，但在 AhR ^-/-小鼠中没有。据我们所知，本研究首次证明了白藜芦醇引起的肝毒性依赖于AhR，而Nrf2在白藜芦醇诱导的氧化性肝损伤的保护中起重要的调节作用。