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Outline
Hepatic injury caused by pyrrolizidine alkaloids (PAs) has attracted widespread global attention. Establishing a rapid evaluation model for PA toxicity is of great significance for risk assessment of PA exposure. Therefore, this study used senecionine as a representative component to investigate its metabolic characteristics in adult zebrafish, providing core metabolic support for the use of the zebrafish model in rapid screening and evaluation of PA toxicity. Adult zebrafish were orally gavaged with senecionine (0.6 mmol·kg-1). Liver tissues were collected at 0.25, 0.5, 1, 2, 6, 12 and 24 hours post-administration. Metabolites were identified using ultra-performance liquid chromatography coupled with tandem mass spectrometry (LC-MSn). Concentration-time profiles of major metabolites were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and pharmacokinetic parameters were fitted. Five metabolites of senecionine were identified in the zebrafish liver, including N-oxide, hydroxylation products, N-glucuronide conjugate of senecionine, and glucuronide conjugate of senecionine hydroxylation product. The parent compound and phase Ⅰ metabolites reached their peaks and were cleared rapidly. Among the phase Ⅱ metabolites, the glucuronide conjugate of the hydroxylation product showed the latest peak and became the predominant form in the zebrafish liver at later time points. This study for the first time systematically elucidated the metabolic profile and kinetic patterns of senecionine in adult zebrafish, confirming that zebrafish possess glucuronidation detoxification capabilities similar to humans. These findings provide a crucial experimental basis for using zebrafish as a model for PA metabolism and toxicity studies, and also offer scientific data for the risk assessment of traditional Chinese medicine preparations containing PAs. This experiment was approved by the Laboratory Animal Ethics Committee of Zhejiang University (Grant No: ZJU20250602).
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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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