Unraveling the liver metabolomic profile of ADB-BUTINACA-induced hepatotoxicity
ADB-BUTINACA, as a new psychoactive substance, can induce physical and psychological dependence. However, the systemic biological impact of ADB-BUTINACA on hepatic metabolomics remains uncertain. The metabolic spectrum in rat livers following exposure to three varying doses of ADB-BUTINACA (0.1, 1,...
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Elsevier
2024-12-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324014519 |
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| author | Yilei Fan Yingyu Huang Yi Zhou Xing Ke Yimei Tian Siyue Zheng Yang Sun Zhongping Huang Jing Zhou Li Wu |
| author_facet | Yilei Fan Yingyu Huang Yi Zhou Xing Ke Yimei Tian Siyue Zheng Yang Sun Zhongping Huang Jing Zhou Li Wu |
| author_sort | Yilei Fan |
| collection | DOAJ |
| description | ADB-BUTINACA, as a new psychoactive substance, can induce physical and psychological dependence. However, the systemic biological impact of ADB-BUTINACA on hepatic metabolomics remains uncertain. The metabolic spectrum in rat livers following exposure to three varying doses of ADB-BUTINACA (0.1, 1, and 5 mg/kg·bw) were analyzed using ultra-high-performance liquid chromatography coupled with high-resolution quadrupole-orbitrap mass spectrometry and molecular docking techniques. Non-target metabolomic technology demonstrated that ADB-BUTINACA induced significant changes in 42 metabolites and disturbed 11 metabolic pathways especially the taurine and hypotaurine metabolism, β-alanine metabolism, and arachidonic acid metabolism, implicates the potential for ADB-BUTINACA to induce not merely cardiac dysfunction but also neurological anomalies. Molecular docking into the hepatotoxic targets of ADB-BUTINACA unveiled its potential for competitive binding with pantetheinase. This interaction may disrupt the coenzyme A (CoA) synthesis pathway, resulting in energy and lipid metabolism imbalances, and ultimately causing hepatotoxic effects. Cellular experiments confirmed reduced HepG2 cell viability and elevated reactive oxygen species (ROS) levels in HepG2 and Huh7 cells. These findings align with our metabolomic findings, supporting the hypothesis that ADB-BUTINACA induces hepatotoxicity via oxidative stress, as well as disruptions in energy and lipid metabolism. This work not only broadens the knowledge of ADB-BUTINACA’ toxicological profile but also contributes to efforts aimed at diagnosing and preventing ADB-BUTINACA-induced hepatotoxicity. |
| format | Article |
| id | doaj-art-0c7399297fb64a7bb361decd05cb4998 |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-0c7399297fb64a7bb361decd05cb49982025-08-20T02:21:04ZengElsevierEcotoxicology and Environmental Safety0147-65132024-12-0128811737510.1016/j.ecoenv.2024.117375Unraveling the liver metabolomic profile of ADB-BUTINACA-induced hepatotoxicityYilei Fan0Yingyu Huang1Yi Zhou2Xing Ke3Yimei Tian4Siyue Zheng5Yang Sun6Zhongping Huang7Jing Zhou8Li Wu9Key Laboratory of Drug Prevention and Control Technology of Zhejiang Province, Zhejiang Police College, Hangzhou 310053, China; College of Pharmaceutical Science & Green Pharmaceutical Collaborative Innovation Center of Yangtze River Delta Region, Zhejiang University of Technology, Hangzhou 310053, ChinaDepartment of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, ChinaNational Narcotics Laboratory Zhejiang Regional Center, Hangzhou 310053, ChinaKey Laboratory of Drug Prevention and Control Technology of Zhejiang Province, Zhejiang Police College, Hangzhou 310053, ChinaDepartment of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, ChinaCollege of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, ChinaHangzhou Bodu Metrology Technology Co., Ltd, Hangzhou 310014, ChinaCollege of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, ChinaKey Laboratory of Drug Prevention and Control Technology of Zhejiang Province, Zhejiang Police College, Hangzhou 310053, China; Corresponding authors.National Narcotics Laboratory Zhejiang Regional Center, Hangzhou 310053, China; Corresponding authors.ADB-BUTINACA, as a new psychoactive substance, can induce physical and psychological dependence. However, the systemic biological impact of ADB-BUTINACA on hepatic metabolomics remains uncertain. The metabolic spectrum in rat livers following exposure to three varying doses of ADB-BUTINACA (0.1, 1, and 5 mg/kg·bw) were analyzed using ultra-high-performance liquid chromatography coupled with high-resolution quadrupole-orbitrap mass spectrometry and molecular docking techniques. Non-target metabolomic technology demonstrated that ADB-BUTINACA induced significant changes in 42 metabolites and disturbed 11 metabolic pathways especially the taurine and hypotaurine metabolism, β-alanine metabolism, and arachidonic acid metabolism, implicates the potential for ADB-BUTINACA to induce not merely cardiac dysfunction but also neurological anomalies. Molecular docking into the hepatotoxic targets of ADB-BUTINACA unveiled its potential for competitive binding with pantetheinase. This interaction may disrupt the coenzyme A (CoA) synthesis pathway, resulting in energy and lipid metabolism imbalances, and ultimately causing hepatotoxic effects. Cellular experiments confirmed reduced HepG2 cell viability and elevated reactive oxygen species (ROS) levels in HepG2 and Huh7 cells. These findings align with our metabolomic findings, supporting the hypothesis that ADB-BUTINACA induces hepatotoxicity via oxidative stress, as well as disruptions in energy and lipid metabolism. This work not only broadens the knowledge of ADB-BUTINACA’ toxicological profile but also contributes to efforts aimed at diagnosing and preventing ADB-BUTINACA-induced hepatotoxicity.http://www.sciencedirect.com/science/article/pii/S0147651324014519ADB-BUTINACANon-targeted metabolomicsMultivariate statistical analysisUHPLC-Q-Orbitrap-HRMSMolecular DockingHepatotoxicity |
| spellingShingle | Yilei Fan Yingyu Huang Yi Zhou Xing Ke Yimei Tian Siyue Zheng Yang Sun Zhongping Huang Jing Zhou Li Wu Unraveling the liver metabolomic profile of ADB-BUTINACA-induced hepatotoxicity Ecotoxicology and Environmental Safety ADB-BUTINACA Non-targeted metabolomics Multivariate statistical analysis UHPLC-Q-Orbitrap-HRMS Molecular Docking Hepatotoxicity |
| title | Unraveling the liver metabolomic profile of ADB-BUTINACA-induced hepatotoxicity |
| title_full | Unraveling the liver metabolomic profile of ADB-BUTINACA-induced hepatotoxicity |
| title_fullStr | Unraveling the liver metabolomic profile of ADB-BUTINACA-induced hepatotoxicity |
| title_full_unstemmed | Unraveling the liver metabolomic profile of ADB-BUTINACA-induced hepatotoxicity |
| title_short | Unraveling the liver metabolomic profile of ADB-BUTINACA-induced hepatotoxicity |
| title_sort | unraveling the liver metabolomic profile of adb butinaca induced hepatotoxicity |
| topic | ADB-BUTINACA Non-targeted metabolomics Multivariate statistical analysis UHPLC-Q-Orbitrap-HRMS Molecular Docking Hepatotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324014519 |
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