Hepatoprotective effect of Artemisia Argyi essential oil on bisphenol A‐induced hepatotoxicity via inhibition of ferroptosis in mice

Abstract

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 Fe2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA‐induced hepatotoxicity by reversing the occurrence of ferroptosis.

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“…Finally, the dried residues from the two steps were combined and redissolved in 50 μL of methanolic solution containing 13 isotopic labels, respectively. 21 The isotopically labelled internal standard compounds were consistent with previous studies. 22…”

“…The MS 2 ( m / z and ionic intensity) was matched to the Main Standard Library standard map to output a data sheet containing information such as compound name, retention time, mass-to-charge ratio, peak area, CAS number, and so on. 21,22 The resultant data matrices were imported into SIMCA software (version 14.1, Umetrics, Sweden) for multivariate statistical analysis, including principal component analysis (PCA) and the orthogonal partial least-squares discriminant analysis (OPLS-DA). Before multivariate statistical analysis, all variables obtained from the LC-MS datasets were mean-centered and scaled to Pareto variance.…”

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