9-Glutathiony1-6,7-dihydro-1-hydroxymethy1-5H-pyrrolizine Is the Major Pyrrolic Glutathione Conjugate of Retronecine-Type Pyrrolizidine Alkaloids in Liver Microsomes and in Rats
文献类型：期刊论文
| 作者 | Chen, Meixia3; Li, Liang3 ; Zhong, Dafang3; Shen, Shuijie2; Zheng, Jiang1,2; Chen, Xiaoyan3
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| 刊名 | CHEMICAL RESEARCH IN TOXICOLOGY
 |
| 出版日期 | 2016-02 |
| 卷号 | 29期号:2页码:180-189 |
| ISSN号 | 0893-228X |
| DOI | 10.1021/acs.chemrestox.5b00427 |
| 文献子类 | Article |
| 英文摘要 | Retronecine-, otonecine-, and heliotridine-type pyrrolizidine alkaloids (PAs) are all reported to be hepatotoxic. These PAs are suggested to be metabolized to the corresponding electrophilic dehydropyrrolizidine alkaloids (dehydro-PAs) and subsequently conjugated with macromolecules, such as glutathione (GSH). In the present study, a total of five glutathione conjugates, named M1-M5, were detected in rat and human liver microsomal incubations with three retrornecine-type PAs (isoline, retrorsine, or monocrotaline) in the presence of glutathione, and were chemically synthesized. M1 and M3 were unambiguously identified as a pair of epimers of 7-glutathionyl-6,7-dihydro-1-hydroxymethyl-SH-pyrrolizine (7-GSH-DHP), and M4 and MS were epimers of 7,9-diglutathiony1-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (7,9-diGSH-DHP). M2, an extremely unstable conjugate, was proposed to be 9-glutathionyl-6,7-dihydro-1-hydroxymethyl-5H-pyrrolizine (9-GSH-DHP). It was the most abundant among the five GSH conjugates, and the finding corrects the mistake that 7-GSH-DHP is the predominant GSH conjugate derived from dehydro-PAs. Similar patterns in glutathione conjugate profile were observed in the bile of rats treated with the PAs. This is the first study to describe 9-GSH-DHP as a major pyrrolic GSH conjugate of retronecine-type PAs, providing insight into the interactions of dehydro-PAs with biomolecules. |
| WOS关键词 | DNA-ADDUCTS ; METABOLIC-ACTIVATION ; SPECIES-DIFFERENCES ; C-14 MONOCROTALINE ; MASS-SPECTROMETRY ; IN-VITRO ; CLIVORINE ; TOXICITY ; TUMORIGENICITY ; HEPATOTOXICITY |
| 资助项目 | National Natural Science Foundation of China[81173115] ; National Natural Science Foundation of China[81430086] ; National Natural Science Foundation of China[81373471] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000370395100007 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276159]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Zheng, Jiang; Chen, Xiaoyan |
| 作者单位 | 1.Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drug Design & Discovery, Shenyang, Peoples R China 2.Univ Washington, Dept Pediat, Div Gastroenterol & Hepatol, Ctr Dev Therapeut,Seattle Childrens Res Inst, Seattle, WA 98195 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chen, Meixia,Li, Liang,Zhong, Dafang,et al. 9-Glutathiony1-6,7-dihydro-1-hydroxymethy1-5H-pyrrolizine Is the Major Pyrrolic Glutathione Conjugate of Retronecine-Type Pyrrolizidine Alkaloids in Liver Microsomes and in Rats[J]. CHEMICAL RESEARCH IN TOXICOLOGY,2016,29(2):180-189. |
| APA | Chen, Meixia,Li, Liang,Zhong, Dafang,Shen, Shuijie,Zheng, Jiang,&Chen, Xiaoyan.(2016).9-Glutathiony1-6,7-dihydro-1-hydroxymethy1-5H-pyrrolizine Is the Major Pyrrolic Glutathione Conjugate of Retronecine-Type Pyrrolizidine Alkaloids in Liver Microsomes and in Rats.CHEMICAL RESEARCH IN TOXICOLOGY,29(2),180-189. |
| MLA | Chen, Meixia,et al."9-Glutathiony1-6,7-dihydro-1-hydroxymethy1-5H-pyrrolizine Is the Major Pyrrolic Glutathione Conjugate of Retronecine-Type Pyrrolizidine Alkaloids in Liver Microsomes and in Rats".CHEMICAL RESEARCH IN TOXICOLOGY 29.2(2016):180-189. |
入库方式： OAI收割
来源：上海药物研究所
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