Kinetic study of pyrrolizidine alkaloid-derived pyrrole-protein adducts in rats after intragastric administration of Gynura japonica
10.16438/j.0513-4870.2019-0772
- VernacularTitle:大鼠灌胃菊三七生成吡咯蛋白加合物的药代动力学研究
- Author:
Yan CHEN
1
;
Xun-jiang WANG
1
;
Fen XIONG
1
;
Wei-qian WANG
1
;
Li YANG
1
,
2
,
3
;
Ai-zhen XIONG
1
;
Chang-hong WANG
1
;
Zheng-tao WANG
1
,
2
,
3
Author Information
1. The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2. Shanghai R &
3. D Center for Standardization of Traditional Chinese Medicines, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
italic>Gynura japonica;
pyrrolizidine alkaloid;
hepatic sinusoidal obstruction syndrome;
pyrrole-protein adduct;
inetic study
- From:
Acta Pharmaceutica Sinica
2020;55(3):473-477
- CountryChina
- Language:Chinese
-
Abstract:
Recently, hepatic sinusoidal obstruction syndrome (HSOS) induced by misuse of Gynura japonica has increased and gained global attention. Large amounts of pyrrolizidine alkaloids (PAs) are present in G. japonica; these PAs are metabolically activated to generate pyrrole-protein adducts (PPAs). In this study, male SD rats were treated orally with a single dose of G. japonica extract (GJE) at 0.062 5, 0.25, 0.5, 1, and 2 g·kg-1. Blood was collected from the orbital venous plexus at 2, 12, 24 and 48 h, and at 48 h after treatment the rats were anesthetized with isoflurane and livers were collected for hematoxylin & eosin staining. The kinetics of PPAs at different doses were studied at 10, 20, 30 min, 1, 2, 4, 6, 12, 24 h, and 48 h, after a single gavage of GJE. The experimental scheme was approved by the ethics committee of animal experiments of Shanghai University of Traditional Chinese Medicine (PZSHUTCM190912019). The concentration of PPAs in serum was determined by liquid chromatography-mass spectrometry (LC-MS). Kinetic data were processed by using the non-compartmental pharmacokinetics data analysis software program PK solutions 2™. The results demonstrate that the concentration of PPAs increased with the dose of GJE and positively correlated with the severity of liver injury. The elimination rate of PPAs in rats was significantly prolonged at higher doses. The level of PPAs and their clearance rate may serve as useful references for the detoxification of PAs-induced injuries.
