Institute of Molecular Biology and Biophysics, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia.
Institute of Cytology and Genetics, Russian Academy of Sciences, Siberian Department, Novosibirsk, Russia.
Drug Chem Toxicol. 2022 Jul;45(4):1587-1596. doi: 10.1080/01480545.2020.1849270. Epub 2020 Nov 19.
Arylamines and polycyclic aromatic hydrocarbons (PAHs) are hazardous anthropogenic pollutants in the environment. The toxicity of PAHs, which include benzo(α)pyrene (BP), is mediated by the activation of Р450 cytochromes of the 1А subfamily (CYP1A1 and CYP1A2). Previously, we have demonstrated that tocopherol, quercetin, and menadione inhibit the expression and activity of CYP1A in the liver of male Wistar rats after administration of a high BP dose to the rats for 3 days. Here, we confirmed the effects of tocopherol, quercetin, and menadione on the expression and activity of CYP1A and on rat liver morphology during prolonged administration (90 days) of a low BP dose. We revealed that subchronic oral administration of a low BP dose has no influence on CYP1A expression as compared to controls but can cause pathomorphological changes in rat liver tissue. These changes are abrogated by tocopherol, attenuated by quercetin, and enhanced by menadione.
芳基胺和多环芳烃 (PAHs) 是环境中有害的人为污染物。包括苯并 (α) 芘 (BP) 在内的 PAHs 的毒性是通过 P450 细胞色素 1A 亚家族 (CYP1A1 和 CYP1A2) 的激活介导的。此前，我们已经证明，生育酚、槲皮素和维生素 K3 在雄性 Wistar 大鼠给予高剂量 BP 3 天后，可抑制 CYP1A 在肝脏中的表达和活性。在这里，我们在大鼠给予低剂量 BP （90 天）的长时间给药过程中，确认了生育酚、槲皮素和维生素 K3 对 CYP1A 的表达和活性以及大鼠肝脏形态的影响。结果显示，与对照组相比，亚慢性口服低剂量 BP 给药对 CYP1A 的表达没有影响，但会引起大鼠肝组织的病理形态变化。这些变化可被生育酚消除，被槲皮素减弱，被维生素 K3 增强。
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