新型有机硒类抗肿瘤化合物WB硒啉在体内组织分布研究

doi:10.5246/jcps.2011.06.074

新型有机硒类抗肿瘤化合物WB硒啉在体内组织分布研究

李叶桓, 张国州, 黄荣华, 李冬冬, 罗钰, 杨勇, 吴银群, 刘丽慧, 曾慧慧^*

1. 北京大学医学部天然药物及仿生药物国家重点实验室; 药学院化学生物学系, 北京 100191
2. 天津国际生物医药联合研究院, 天津 300457

收稿日期:2011-06-02 修回日期:2011-09-02 出版日期:2011-11-15 发布日期:2011-11-15
通讯作者: 曾慧慧*

Study on tissue distribution of a novel organoselenium antitumor compound WBSELEN

Ye-Huan Li, Guo-Zhou Zhang, Rong-Hua Huang, Dong-Dong Li, Yu Luo, Yong Yang, Yin-Qun Wu, Li-Hui Liu, Hui-Hui Zeng^*

1. State Key Laboratory of Natural and Biomimetic Drugs; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Tianjin International Joint Academy of Biotechnology & Medicine, Tianjin 300457, China

Received:2011-06-02 Revised:2011-09-02 Online:2011-11-15 Published:2011-11-15
Contact: Hui-Hui Zeng*

摘要/Abstract

摘要：

本研究首次对新型有机硒类抗肿瘤化合物1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]pentane (WB)进行组织分布特点研究。将H22荷瘤小鼠单次和连续多次灌胃给药WB (120 mg/kg/d) 4小时后, 用氢化物发生原子荧光光谱法(AFS) 测定组织、血浆、肿瘤中的硒含量, 考察WB的组织分布特点。经测定发现肝脏和胃肠道的硒含量显著升高, 心、脾、肺、胰、血浆、肿瘤的硒含量也有不同程度的升高, 脑和肾的硒含量基本无变化, 两种给药方式引起的各组织硒含量变化无显著性差异。结果表明: WB及其代谢物在肝和胃肠道有靶向摄入, 在其他器官也有不同程度的摄入, 但WB无明显蓄积表现。

关键词: 有机硒化合物, 抗肿瘤, 组织分布, 氢化物原子荧光光谱

Abstract: A novel organoselenium compound, WB (1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]pentane) has indicated anti-tumor activity. Its pharmacokinetic data has never been determined. By using the H22 tumor bearing mouse model, the tissue distribution of WB after single and four consecutive doses (both were 120 mg/kg/d) was explored. The selenium content of the tissues was used as an indicator of WB absorption, distribution and metabolism. The selenium in the heart, liver, spleen, kidneys, lungs, stomach, pancreas, brain, colon, intestine, testes, plasma, and tumor were determined by generation atomic fluorescence spectrometry (AFS). With single or multiple oral administration of WB, the selenium content significantly increased in the liver, stomach, colon, and intestine. The selenium content in the spleen, lungs, pancreas, testes, plasma and tumor also increased compared with the controls; but no significant changes were found in the brain and kidney. WB and its metabolites distributed predominantly in the colon, liver, stomach and intestine, which resulted in a significant increase in the selenium content in both groups. There was no observed significant accumulation of WB in the vital organs.

Key words: Organoselenium compound, Antitumor, Tissue distribution, Hydride generation atomic fluorescence spectrometry

中图分类号:

R969.1

Supporting:

Foundation item: National Major Projects on Drug Research and Technology (Grant No. 2009ZX09103-032).
^*Corresponding author. Tel.: 86-10-82802878

李叶桓, 张国州, 黄荣华, 李冬冬, 罗钰, 杨勇, 吴银群, 刘丽慧, 曾慧慧^*. 新型有机硒类抗肿瘤化合物WB硒啉在体内组织分布研究[J]. , DOI: 10.5246/jcps.2011.06.074.

Ye-Huan Li, Guo-Zhou Zhang, Rong-Hua Huang, Dong-Dong Li, Yu Luo, Yong Yang, Yin-Qun Wu, Li-Hui Liu, Hui-Hui Zeng^*. Study on tissue distribution of a novel organoselenium antitumor compound WBSELEN[J]. , DOI: 10.5246/jcps.2011.06.074.

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