Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism

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• 作者：Xue Shao^a ; Zhengtao Hu^a ; Chunyan Hu^a ; Qian Bu^a ; Guangyan Yan^a ; Pengchi Deng^b ; Lei Lv^a ; Dan Wu^c ; Yi Deng^a ; Jinxuan Zhao^a ; Ruiming Zhu^a ; Yan Li^a ; Hongyu Li^a ; Youzhi Xu^a ; Hanshuo Yang^a ; Yinglan Zhao^a ; Xiaobo Cen^a ; ^{xbcenalan@vip.sina.com}
• 关键词：Metabonomics ; Antioxidants ; Angiogenesis ; Malformation
• 刊名：Toxicology and Applied Pharmacology
• 出版年：2012
• 期刊代码：58_0041008x
• 类别：pha
• 出版时间：1 May, 2012
• 卷：260
• 期：3
• 页码：260-270
• 文件大小：1763 K

摘要

Investigations have characterized addictive drug-induced developmental cardiovascular malformation in human, non-human primate and rodent. However, the underlying mechanism of malformation caused by drugs during pregnancy is still largely unknown, and preventive and therapeutic measures have been lacking. Using ¹H NMR spectroscopy, we profiled the metabolites from human embryo endothelial cells exposed to methamphetamine (METH) and quantified a total of 226 peaks. We identified 11 metabolites modified robustly and found that taurine markedly increased. We then validated the hypothesis that this dramatic increase in taurine could attribute to its effect in inhibiting METH-induced developmental angiogenesis defect. Taurine supplement showed a more significant potential than other metabolites in protecting against METH-induced injury in endothelial cells. Taurine strongly attenuated METH-induced inhibition of proliferation and migration in endothelial cells. Furthermore, death rate and vessel abnormality of zebrafish embryos treated with METH were greatly reversed by taurine. In addition, taurine supplement caused a rapid decrease in reactive oxygen species generation and strongly attenuated the excitable arise of antioxidase activities in the beginning of METH exposure prophase. Dysregulations of NF-魏B, p-ERK as well as Bax, which reflect apoptosis, cell cycle arrest and oxidative stress in vascular endothelium, were blocked by taurine. Our results provide the first evidence that taurine prevents METH-caused developmental angiogenesis defect through antioxidant mechanism. Taurine could serve as a potential therapeutic or preventive intervention of developmental vascular malformation for the pregnant women with drug use.