Unexpected low-dose toxicity of the universal solvent DMSO
Unexpected low-dose toxicity of the universal solvent DMSO
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DOI：
10.1096/fj.13-235440
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发表时间：
2014-03-01
期刊：
影响因子：
4.8
通讯作者：
Cordeiro, M. Francesca
中科院分区：
文献类型：
--
作者：
Galvao, Joana;Davis, Benjamin;Cordeiro, M. Francesca
二甲亚砜 (DMSO) 是一种重要的非质子溶剂，可以溶解多种难溶的极性和非极性分子。再加上其在浓度 1% (v/v) 时的明显低毒性，使用膜联蛋白 V、末端脱氧核苷酸转移酶 dUTP 缺口末端标记 (TUNEL)、3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 和 AlamarBlue 细胞活力测定。最近有报道称，DMSO 浓度 >10% (v/v) 会通过质膜孔形成而引起细胞毒性。在这里，我们展示了低浓度 (2-4% DMSO) 诱导 caspase-3 独立神经元死亡的机制，其中涉及凋亡诱导因子 (AIF) 从线粒体易位到细胞核和聚 (ADP-核糖)-聚合酶 (PARP) 激活。这些结果凸显了使用低浓度 DMSO 作为体内给药和生物测定溶剂的安全问题。我们建议采用 DMSO 以外的方法来溶解药物，但在没有其他选择的情况下，研究人员计算绝对 DMSO 最终浓度，并除了 DMSO 载体对照外还包括未经处理的对照组，以检查溶剂毒性。 Galvao, J.、Davis, B.、Tilley, M.、Normando, E.、Duchen, M. R.、Cordeiro, M. F. 通用药物的意外低剂量毒性 溶剂二甲基亚砜。
Dimethyl sulfoxide (DMSO) is an important aprotic solvent that can solubilize a wide variety of otherwise poorly soluble polar and nonpolar molecules. This, coupled with its apparent low toxicity at concentrations 1% (v/v), using annexin V, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and AlamarBlue cell viability assays. DMSO concentrations >10% (v/v) have recently been reported to cause cellular toxicity through plasma membrane pore formation. Here, we show the mechanism by which low concentrations (2-4% DMSO) induce caspase-3 independent neuronal death that involves apoptosis-inducing factor (AIF) translocation from mitochondria to the nucleus and poly-(ADP-ribose)-polymerase (PARP) activation. These results highlight safety concerns of using low concentrations of DMSO as a solvent for in vivo administration and in biological assays. We recommend that methods other than DMSO are employed for solubilizing drugs but, where no alternative exists, researchers compute absolute DMSO final concentrations and include an untreated control group in addition to DMSO vehicle control to check for solvent toxicity.Galvao, J., Davis, B., Tilley, M., Normando, E., Duchen, M. R., Cordeiro, M. F. Unexpected low-dose toxicity of the universal solvent DMSO.