Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism.

Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism.
复制标题

牛磺酸通过抗氧化机制保护甲基苯丙胺诱导的发育性血管生成缺陷。

DOI:
10.1016/j.taap.2012.03.003
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发表时间:
2012-05
期刊:
Toxicol Appl Pharmacol (IF 4.447)
影响因子:
--
通讯作者:
Deng Y
Deng Y
中科院分区:
其他
文献类型:
--
作者:
Shao X;Zhao J;Zhu R;Li Y;Li H;Xu Y;Yang H;Zhao Y;Cen X;Hu Z;Hu C;Bu Q;Yan G;Deng P;Lv L;Wu D;Deng Y

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研究表明,人类、非人类灵长类动物和啮齿类动物中成瘾药物诱发的心血管发育畸形。然而,妊娠期间药物导致畸形的根本机制尚不清楚,也缺乏预防和治疗措施。我们利用 1 H NMR 光谱分析了暴露于甲基苯丙胺 (METH) 的人胚胎内皮细胞的代谢物,并对总共 226 个峰进行了定量。我们鉴定了 11 种经过严格修饰的代谢物,发现牛磺酸显着增加。然后,我们验证了这样的假设:牛磺酸的显着增加可能归因于其抑制冰毒诱导的发育性血管生成缺陷的作用。牛磺酸补充剂在预防冰毒引起的内皮细胞损伤方面比其他代谢物表现出更显着的潜力。牛磺酸强烈减弱冰毒诱导的内皮细胞增殖和迁移抑制。此外,牛磺酸大大逆转了用METH处理的斑马鱼胚胎的死亡率和血管异常。此外,牛磺酸的补充导致活性氧生成迅速减少,并强烈减弱了冰毒暴露前期抗氧化酶活性的兴奋性产生。 NF-κB、p-ERK 和 Bax 的失调反映了血管内皮细胞的细胞凋亡、细胞周期停滞和氧化应激,牛磺酸可以阻断这些失调。我们的研究结果提供了第一个证据,证明牛磺酸通过抗氧化机制预防冰毒引起的发育性血管生成缺陷。牛磺酸可以作为吸毒孕妇发育性血管畸形的潜在治疗或预防干预措施。
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. Using1H 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-κB, 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.
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