Premium
Comparative metabolism of gelsenicine in liver microsomes from humans, pigs, goats and rats
Author(s) -
Wang ZiYuan,
Zuo MingTing,
Zhao XueJiao,
Li YuJuan,
Sun ZhiLiang,
Liu ZhaoYing
Publication year - 2020
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.8843
Subject(s) - chemistry , microsome , demethylation , high performance liquid chromatography , chromatography , metabolism , tandem mass spectrometry , microsoma , alkaloid , mass spectrometry , metabolite , liquid chromatography–mass spectrometry , biochemistry , in vitro , stereochemistry , gene expression , dna methylation , gene
Rationale Gelsemium elegans ( G. elegans ) is highly toxic to humans and rats but has insecticidal and growth‐promoting effects on pigs and goats. However, the mechanisms behind the toxicity differences of G. elegans are unclear. Gelsenicine, isolated from G. elegans , has been reported to be a toxic alkaloid. Methods In this study, the in vitro metabolism of gelsenicine was investigated and compared for the first time using human (HLM), pig (PLM), goat (GLM) and rat (RLM) liver microsomes and high‐performance liquid chromatography/mass spectrometry (HPLC/MS). Results In total, eight metabolites ( M1 – M8 ) were identified by using high‐performance liquid chromatography/quadrupole‐time‐of‐flight mass spectrometry (HPLC/QqTOF‐MS). Two main metabolic pathways were found in the liver microsomes of the four species: demethylation at the methoxy group on the indole nitrogen ( M1 ) and oxidation at different positions ( M2 – M8 ). M8 was identified only in the GLM. The degradation ratio of gelsenicine and the relative percentage of metabolites produced during metabolism were determined by high‐performance liquid chromatography/tandem mass spectrometry (HPLC/QqQ‐MS/MS). The degradation ratio of gelsenicine in liver microsomes decreased in the following order: PLM ≥ GLM > HLM > RLM. The production of M1 decreased in the order of GLM > PLM > RLM > HLM, the production of M2 was similar among the four species, and the production of M3 was higher in the HLM than in the liver microsomes of the other three species. Conclusions Based on these results, demethylation was speculated to be the main gelsenicine detoxification pathway, providing vital information to better understand the metabolism and toxicity differences of G. elegans among different species.