Gestational and Lactational Co-Exposure to DEHP and BPA Impairs Hepatic Function via PI3K/AKT/FOXO1 Pathway in Offspring
Di-(2-Ethylhexyl) phthalate (DEHP) and bisphenol A (BPA) present significant environmental endocrine-disrupting chemical properties. Although studies have implied reproductive impairment from exposure to BPA and DEHP, no study to date has shown the effect and mechanism of hepatic function after gest...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/3/216 |
| _version_ | 1797608875841552384 |
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| author | Minghan Wang Yu Wang Junyuan Han Zhiwen Duan Jiye Yin Rigao Ding Quanjun Wang |
| author_facet | Minghan Wang Yu Wang Junyuan Han Zhiwen Duan Jiye Yin Rigao Ding Quanjun Wang |
| author_sort | Minghan Wang |
| collection | DOAJ |
| description | Di-(2-Ethylhexyl) phthalate (DEHP) and bisphenol A (BPA) present significant environmental endocrine-disrupting chemical properties. Although studies have implied reproductive impairment from exposure to BPA and DEHP, no study to date has shown the effect and mechanism of hepatic function after gestational and lactational co-exposure to DEHP and BPA in offspring. A total of 36 perinatal rats were randomly divided into four groups, DEHP (600 mg/kg/day), BPA (80 mg/kg/day), DEHP combined with BPA (600 mg/kg/day + 80 mg/kg/day), and control. Notably, 11 chemical targets were screened after identifying eight substances associated with chemically-induced hepatic damage. Molecular docking simulations revealed a high-scoring combination of eight metabolic components and targets of the PI3K/AKT/FOXO1 signaling pathway. The DEHP and BPA combination disrupted hepatic steatosis, ultimately affecting systemic the glucose and the lipid metabolic homeostasis with significant toxicity. Mechanistically, co-exposure to DEHP and BPA causes liver dysfunction and hepatic insulin resistance via PI3K/AKT/FOXO1 pathway in offspring. This is the first study of the hepatic function and mechanism of co-exposure to DEHP and BPA that combines metabolomics, molecular docking, and traditional toxicity assessment methods. |
| first_indexed | 2024-03-11T05:49:41Z |
| format | Article |
| id | doaj.art-de8783a5112241cdbd97e1ecc984f2a5 |
| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-11T05:49:41Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxics |
| spelling | doaj.art-de8783a5112241cdbd97e1ecc984f2a52023-11-17T14:12:45ZengMDPI AGToxics2305-63042023-02-0111321610.3390/toxics11030216Gestational and Lactational Co-Exposure to DEHP and BPA Impairs Hepatic Function via PI3K/AKT/FOXO1 Pathway in OffspringMinghan Wang0Yu Wang1Junyuan Han2Zhiwen Duan3Jiye Yin4Rigao Ding5Quanjun Wang6State key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100089, ChinaFaculty of Life Sciences, China Medical University, Shenyang 110031, ChinaState key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100089, ChinaShenyang Medical College, School of Public Health, Shenyang 110121, ChinaState key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100089, ChinaState key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100089, ChinaState key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100089, ChinaDi-(2-Ethylhexyl) phthalate (DEHP) and bisphenol A (BPA) present significant environmental endocrine-disrupting chemical properties. Although studies have implied reproductive impairment from exposure to BPA and DEHP, no study to date has shown the effect and mechanism of hepatic function after gestational and lactational co-exposure to DEHP and BPA in offspring. A total of 36 perinatal rats were randomly divided into four groups, DEHP (600 mg/kg/day), BPA (80 mg/kg/day), DEHP combined with BPA (600 mg/kg/day + 80 mg/kg/day), and control. Notably, 11 chemical targets were screened after identifying eight substances associated with chemically-induced hepatic damage. Molecular docking simulations revealed a high-scoring combination of eight metabolic components and targets of the PI3K/AKT/FOXO1 signaling pathway. The DEHP and BPA combination disrupted hepatic steatosis, ultimately affecting systemic the glucose and the lipid metabolic homeostasis with significant toxicity. Mechanistically, co-exposure to DEHP and BPA causes liver dysfunction and hepatic insulin resistance via PI3K/AKT/FOXO1 pathway in offspring. This is the first study of the hepatic function and mechanism of co-exposure to DEHP and BPA that combines metabolomics, molecular docking, and traditional toxicity assessment methods.https://www.mdpi.com/2305-6304/11/3/216di-(2-ethylhexyl) phthalatebisphenol Amixture toxicitymetabolomicsPI3K/AKT/FOXO1 signaling pathwaymolecular docking |
| spellingShingle | Minghan Wang Yu Wang Junyuan Han Zhiwen Duan Jiye Yin Rigao Ding Quanjun Wang Gestational and Lactational Co-Exposure to DEHP and BPA Impairs Hepatic Function via PI3K/AKT/FOXO1 Pathway in Offspring Toxics di-(2-ethylhexyl) phthalate bisphenol A mixture toxicity metabolomics PI3K/AKT/FOXO1 signaling pathway molecular docking |
| title | Gestational and Lactational Co-Exposure to DEHP and BPA Impairs Hepatic Function via PI3K/AKT/FOXO1 Pathway in Offspring |
| title_full | Gestational and Lactational Co-Exposure to DEHP and BPA Impairs Hepatic Function via PI3K/AKT/FOXO1 Pathway in Offspring |
| title_fullStr | Gestational and Lactational Co-Exposure to DEHP and BPA Impairs Hepatic Function via PI3K/AKT/FOXO1 Pathway in Offspring |
| title_full_unstemmed | Gestational and Lactational Co-Exposure to DEHP and BPA Impairs Hepatic Function via PI3K/AKT/FOXO1 Pathway in Offspring |
| title_short | Gestational and Lactational Co-Exposure to DEHP and BPA Impairs Hepatic Function via PI3K/AKT/FOXO1 Pathway in Offspring |
| title_sort | gestational and lactational co exposure to dehp and bpa impairs hepatic function via pi3k akt foxo1 pathway in offspring |
| topic | di-(2-ethylhexyl) phthalate bisphenol A mixture toxicity metabolomics PI3K/AKT/FOXO1 signaling pathway molecular docking |
| url | https://www.mdpi.com/2305-6304/11/3/216 |
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