Hanslick Jennifer L, Lau Karen, Noguchi Kevin K, Olney John W, Zorumski Charles F, Mennerick Steven, Farber Nuri B
Department of Psychiatry, Washington University, Saint Louis, Missouri 63110-1093, USA.
Neurobiol Dis. 2009 Apr;34(1):1-10. doi: 10.1016/j.nbd.2008.11.006. Epub 2008 Dec 3.
Dimethyl sulfoxide (DMSO) is a solvent that is routinely used as a cryopreservative in allogous bone marrow and organ transplantation. We exposed C57Bl/6 mice of varying postnatal ages (P0-P30) to DMSO in order to study whether DMSO could produce apoptotic degeneration in the developing CNS. DMSO produced widespread apoptosis in the developing mouse brain at all ages tested. Damage was greatest at P7. Significant elevations above the background rate of apoptosis occurred at the lowest dose tested, 0.3 ml/kg. In an in vitro rat hippocampal culture preparation, DMSO produced neuronal loss at concentrations of 0.5% and 1.0%. The ability of DMSO to damage neurons in dissociated cultures indicates that the toxicity likely results from a direct cellular effect. Because children, who undergo bone marrow transplantation, are routinely exposed to DMSO at doses higher than 0.3 ml/kg, there is concern that DMSO might be producing similar damage in human children.
二甲基亚砜(DMSO)是一种常用于同种异体骨髓和器官移植中的冷冻保护剂。我们将不同出生后年龄(P0 - P30)的C57Bl/6小鼠暴露于二甲基亚砜中,以研究二甲基亚砜是否会在发育中的中枢神经系统中产生凋亡性退变。在所有测试的年龄阶段,二甲基亚砜均在发育中的小鼠脑中产生了广泛的细胞凋亡。在P7时损伤最为严重。在测试的最低剂量0.3 ml/kg时,凋亡率显著高于背景水平。在体外大鼠海马培养物制备中,二甲基亚砜在浓度为0.5%和1.0%时导致神经元损失。二甲基亚砜在解离培养物中损伤神经元的能力表明,其毒性可能源于直接的细胞效应。由于接受骨髓移植的儿童通常会暴露于高于0.3 ml/kg的二甲基亚砜剂量下,因此人们担心二甲基亚砜可能会对人类儿童产生类似的损伤。