The comparative pharmacokinetics of two pyrrolizidine alkaloids, senecionine and adonifoline, and their main metabolites in rats after intravenous and oral administration by UPLC/ESIMS |
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Authors: | Wang Changhong Li Yan Gao Jiangguo He Yuqi Xiong Aizhen Yang Li Cheng Xuemei Ma Yueming Wang Zhengtao |
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Institution: | (1) The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China;(2) Shanghai R&D Center for Standardization of Traditional Chinese Medicines, 199 Guoshoujing Road, Shanghai, 201210, China;(3) College of Pharmacy, Xinjiang Medical University, 8 Xinyi Road, Urumuqi, 830054, China;(4) Laboratory of Pharmacokinetics, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201210, China |
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Abstract: | Pyrrolizidine alkaloids (PAs) are considered to be one of the most hepatotoxic groups of compounds of plant origin and are
present in about 3% of the world’s flowering plants. Most PAs represent a considerable health hazard to both livestock and
humans through the consumption of plants and PA-contaminated products such as milk, honey, herbal teas, and medicines. This
study determined the differences in the in vivo pharmacokinetic behavior of senecionine (SEN), adonifoline (ADO), and their
main metabolites in rats after intravenous administration and oral administration by ultraperformance liquid chromatography/electrospray
ionization mass spectrometry. Upon intravenous administration and oral administration of SEN and ADO, significant differences
in pharmacokinetics were observed, with the SEN and ADO being absorbed fast with lower bioavailability and being quickly metabolized
to PA N-oxides and hydroxylation products of PAs or their N-oxides. It could be seen that the plasma concentration ratio of senecionine N-oxide (SEN-NO) to SEN (C
SEN-NO/C
SEN) was significantly larger than that for adonifoline N-oxide (ADO-NO) and ADO (C
ADO-NO/C
ADO) (P < 0.001) for both dosing routes in rats. The high N-oxygenation activity and extensive toxicity of SEN, compared with ADO, in rats raised the question of whether or not the
higher metabolic rate of SEN in rats in vivo was related to its potent toxicity. The toxicity of SEN-NO and ADO-NO needs to
be evaluated further and compared in vitro/in vivo. This study was most helpful for interpreting the metabolism of metabolic
bioactivation and detoxication, and toxicity differences among SEN, ADO and other PAs. |
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