title: Taurine protects methamphetamine-induced developmental angiogenesis defect through antioxidant mechanism.
abstract: 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-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.
authors.affiliation: National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Shao
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Hu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hu
authors.forename: Qian
authors.initials: Q
authors.lastname: Bu
authors.forename: Guangyan
authors.initials: G
authors.lastname: Yan
authors.forename: Pengchi
authors.initials: P
authors.lastname: Deng
authors.forename: Lei
authors.initials: L
authors.lastname: Lv
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Deng
authors.forename: Jinxuan
authors.initials: J
authors.lastname: Zhao
authors.forename: Ruiming
authors.initials: R
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
authors.forename: Youzhi
authors.initials: Y
authors.lastname: Xu
authors.forename: Hanshuo
authors.initials: H
authors.lastname: Yang
authors.forename: Yinglan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cen
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008694:Methamphetamine / Q000633:toxicity*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D013654:Taurine; D008694:Methamphetamine