Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Henan Joint International Research Laboratory of Chronic Liver Injury, Henan Key Laboratory of Rehabilitation Medicine, Department of Pediatrics, the Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
Environ Toxicol. 2023 Oct;38(10):2416-2428. doi: 10.1002/tox.23877. Epub 2023 Jun 22.
The environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography-mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up-regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA-induced hepatotoxicity by reversing the occurrence of ferroptosis.
环境污染物双酚 A（BPA），用于制造各种饮食的塑料包装材料，广泛分布于环境中，并通过诱导氧化应激引起严重的肝毒性。艾蒿精油（AAEO），一种从艾蒿 H.Lév. & Vaniot 中分离出来的挥发性油成分，具有药理学作用，特别是对肝保护作用。然而，AAEO 在 BPA 诱导的肝毒性中的潜在作用尚未得到表征。首先，我们通过气相色谱-质谱法分析了 AAEO 的化学成分。在此，我们研究了 AAEO 对暴露于 BPA 的小鼠肝代谢变化的影响。结果表明，与 BPA 组相比，AAEO 可降低 BPA 小鼠血清中肝功能酶的水平，并改善肝损伤和纤维化。此外，通过代谢组学筛选出的 20 种差异代谢物主要涉及谷胱甘肽代谢、嘌呤代谢和多不饱和脂肪酸合成的重编程。此外，AAEO 可以减少 BPA 诱导的肝铁死亡，这表现为降低黄嘌呤氧化酶活性，上调谷胱甘肽过氧化物酶 4（GPX4）、超氧化物歧化酶和过氧化氢酶的活性，促进谷胱甘肽的合成，同时抑制转铁蛋白受体 1（TFR1）的表达，以减少细胞内 Fe 的积累。因此，我们的研究表明，AAEO 通过逆转铁死亡的发生，成为一种针对 BPA 诱导的肝毒性的肝保护剂。
