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Synthetic cannabinoid N-(1-carbamoyl-2, 2-dimethylpropyl)-1-butylazole-3-formamide (ADB-BUTINACA), as a new psychoactive substance, shows strong stimulant and hallucinogenic effects. It can cause cardiovascular, renal and gastrointestinal diseases, and in severe cases, it can lead to death. However, there are few reports on toxicology studies of the ADB-BUTINACA metabolic pathway and its long-term effects on the organism and the molecular mechanisms behind it. In this study, the metabolic profile of rat serum after low, medium and high doses of ADB-BUTINACA (0.1, 1, and 5 mg·kg-1) intervention were analyzed using UHPLC coupled with a Q-Orbitrap-MS (UHPLC-Q-Orbitrap-HRMS). The results showed that the intervention of ADB-BUTINACA could cause significant changes of 50 metabolites such as L-glutamate and 3-hydroxybutyrate, and nine metabolic pathways including alanine, aspartate and glutamate metabolism, retinol metabolism, and TCA cycle were disturbed. These findings provide a novel experimental and theoretical framework for further investigation of the toxicological mechanisms underlying ADB-BUTINACA-induced dysregulation of lipid and energy metabolism. Furthermore, they offer valuable insights that could facilitate the diagnosis and prevention of ADB-BUTINACA toxicity, thereby underscoring their significant implications for public health. The study was conducted in adherence to both the Declaration of Helsinki and the National Institutes of Health's Guidelines for the Care and Use of Laboratory Animals, and received approval from the animal experimental center at the Zhejiang Chinese Medical University (Ethical number: 20220718-11).
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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