First evidence of pyrrolizidine alkaloid N-oxide-induced hepatic sinusoidal obstruction syndrome in humans
文献类型：期刊论文
| 作者 | Yang, Mengbi2,4,5; Ruan, Jianqing2,4,5; Gao, Hong3; Li, Na2; Ma, Jiang2,4,5; Xue, Junyi2,4,5; Ye, Yang1,4,5 ; Fu, Peter Pi-Cheng6; Wang, Jiyao3; Lin, Ge2,4,5
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| 刊名 | ARCHIVES OF TOXICOLOGY
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| 出版日期 | 2017-12 |
| 卷号 | 91期号:12页码:3913-3925 |
| 关键词 | Pyrrolizidine alkaloid N-oxide Pyrrolizidine alkaloid Hepatic sinusoidal obstruction syndrome Pyrrole-protein adduct Biotransformation Toxicokinetic |
| ISSN号 | 0340-5761 |
| DOI | 10.1007/s00204-017-2013-y |
| 文献子类 | Article |
| 英文摘要 | Pyrrolizidine alkaloids (PAs) are among the most potent phytotoxins widely distributed in plant species around the world. PA is one of the major causes responsible for the development of hepatic sinusoidal obstruction syndrome (HSOS) and exerts hepatotoxicity via metabolic activation to form the reactive metabolites, which bind with cellular proteins to generate pyrrole-protein adducts, leading to hepatotoxicity. PA N-oxides coexist with their corresponding PAs in plants with varied quantities, sometimes even higher than that of PAs, but the toxicity of PA N-oxides remains unclear. The current study unequivocally identified PA N-oxides as the sole or predominant form of PAs in 18 Gynura segetum herbal samples ingested by patients with liver damage. For the first time, PA N-oxides were recorded to induce HSOS in human. PA N-oxide-induced hepatotoxicity was further confirmed on mice orally dosed of herbal extract containing 170 mu mol PA N-oxides/kg/day, with its hepatotoxicity similar to but potency much lower than the corresponding PAs. Furthermore, toxicokinetic study after a single oral dose of senecionine N-oxide (55 mu mol/kg) on rats revealed the toxic mechanism that PA N-oxides induced hepatotoxicity via their biotransformation to the corresponding PAs followed by the metabolic activation to form pyrrole-protein adducts. The remarkable differences in toxicokinetic profiles of PAs and PA N-oxides were found and attributed to their significantly different hepatotoxic potency. The findings of PA N-oxide-induced hepatotoxicity in humans and rodents suggested that the contents of both PAs and PA N-oxides present in herbs and foods should be regulated and controlled in use. |
| WOS关键词 | INDUCED LIVER-INJURY ; VENOOCCLUSIVE DISEASE ; METABOLIC-ACTIVATION ; DIETARY-SUPPLEMENTS ; MASS-SPECTROMETRY ; HEPATOTOXICITY ; IDENTIFICATION ; QIANLIGUANG ; PRODUCTS ; ENZYMES |
| 资助项目 | Research Grant Council of Hong Kong (GRF)[471013] ; Research Grant Council of Hong Kong (GRF)[14110714] ; One-off Funding for Joint Lab/Research Collaboration by CUHK[3132968] ; CUHK School of Biomedical Sciences-Seed Fund for Joint Establishments[00000000] ; Chinese University of Hong Kong[3132968] ; Chinese University of Hong Kong[4054302] |
| WOS研究方向 | Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000417266400014 |
| 出版者 | SPRINGER HEIDELBERG |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272374]  |
| 专题 | 天然药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Lin, Ge |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res & Nat Prod, Dept Chem, Shanghai, Peoples R China; 2.Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Hong Kong, Hong Kong, Peoples R China; 3.Fudan Univ, Zhongshan Hosp, Div Gastroenterol, Shanghai, Peoples R China; 4.Chinese Acad Sci, Joint Res Lab Promoting Globalizat Tradit Chinese, Hong Kong, Hong Kong, Peoples R China; 5.Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China; 6.Natl Ctr Toxicol Res, Jefferson, AR 72079 USA |
| 推荐引用方式 GB/T 7714 | Yang, Mengbi,Ruan, Jianqing,Gao, Hong,et al. First evidence of pyrrolizidine alkaloid N-oxide-induced hepatic sinusoidal obstruction syndrome in humans[J]. ARCHIVES OF TOXICOLOGY,2017,91(12):3913-3925. |
| APA | Yang, Mengbi.,Ruan, Jianqing.,Gao, Hong.,Li, Na.,Ma, Jiang.,...&Lin, Ge.(2017).First evidence of pyrrolizidine alkaloid N-oxide-induced hepatic sinusoidal obstruction syndrome in humans.ARCHIVES OF TOXICOLOGY,91(12),3913-3925. |
| MLA | Yang, Mengbi,et al."First evidence of pyrrolizidine alkaloid N-oxide-induced hepatic sinusoidal obstruction syndrome in humans".ARCHIVES OF TOXICOLOGY 91.12(2017):3913-3925. |
入库方式： OAI收割
来源：上海药物研究所
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