Covalent protein binding and tissue distribution of houttuynin in rats after intravenous administration of sodium houttuyfonate
文献类型：期刊论文
| 作者 | Deng, Zhi-peng; Zhong, Da-fang ; Meng, Jian; Chen, Xiao-yan
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2012-04 |
| 卷号 | 33期号:4页码:568-576 |
| 关键词 | sodium houttuyfonate houttuynin arginine-specific modification pyrimidine adduct LC/MSn analysis tissue distribution houttuyniae preparations |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2011.174 |
| 文献子类 | Article |
| 英文摘要 | Aim: To investigate the potential of houttuynin to covalently bind to proteins in vitro and in vivo and to identify the adduct structures. Methods: Male Sprague-Dawley rats-were intravenously injected with sodium houttuyfonate (10 mg/kg). The concentrations of houttuynin in blood, plasmaand-five tissues tested were determined using an LC/MS/MS method. The covalent binding values of houttuynin with hemoglobin, plasma and tissue proteins were measured in rats after intravenous injection of [1-14C]sodium houttuyfonate (10 mg/kg, 150 mCi/kg). Human serum albumin was used as model protein to identify the modification site(s) and structure(s) through enzymatic digestion and LC/MS" analysis. Results: The drug was widely distributed 10 min after intravenous injection. The lungs were the preferred site for disposition, followed by the heart and kidneys with significantly higher concentrations than that in the plasma. The extent of covalent binding was correlated with the respective concentrations in the tissues, ranging from 1137 nmol/g protein in lung to 266 nmol/g protein in liver. Houttuynin reacted primarily with arginine residues in human serum albumin to form a pyrimidine adduct at 1:1 molar ratio. The same adduct was detected in rat lungs digested by pronase E. Conclusion: This study showed that the I3-keto aldehyde moiety in houttuynin is strongly electrophilic and readily confers covalent binding to tissue proteins, especially lung proteins, by a Schiff's base mechanism. The findings explain partially the idiosyncratic reactions of houttuyniae injection in clinical use. |
| WOS关键词 | HUMAN SERUM-ALBUMIN ; ACROLEIN ; ARGININE ; ADDUCTS |
| 资助项目 | National Natural Science Foundation of China[90709036] ; National Natural Science Foundation of China[81173117] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4491954 |
| WOS记录号 | WOS:000302586900018 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278137]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Chen, Xiao-yan |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Deng, Zhi-peng,Zhong, Da-fang,Meng, Jian,et al. Covalent protein binding and tissue distribution of houttuynin in rats after intravenous administration of sodium houttuyfonate[J]. ACTA PHARMACOLOGICA SINICA,2012,33(4):568-576. |
| APA | Deng, Zhi-peng,Zhong, Da-fang,Meng, Jian,&Chen, Xiao-yan.(2012).Covalent protein binding and tissue distribution of houttuynin in rats after intravenous administration of sodium houttuyfonate.ACTA PHARMACOLOGICA SINICA,33(4),568-576. |
| MLA | Deng, Zhi-peng,et al."Covalent protein binding and tissue distribution of houttuynin in rats after intravenous administration of sodium houttuyfonate".ACTA PHARMACOLOGICA SINICA 33.4(2012):568-576. |
入库方式： OAI收割
来源：上海药物研究所
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