Pagán Oné R, Rowlands Amanda L, Urban Kimberly R
Department of Biology, West Chester University, West Chester, PA 19383-2112, USA.
Neurosci Lett. 2006 Oct 30;407(3):274-8. doi: 10.1016/j.neulet.2006.08.073. Epub 2006 Sep 18.
In this work, we describe aspects of the toxicity and behavioral effects of dimethylsulfoxide (DMSO) in planaria. Planarian worms have traditionally been a favored animal model in developmental biology. More recently, this organism is being recognized as an animal model in neuropharmacology research. DMSO is often used in cell and tissue culture as a cryoprotectant agent and is also commonly used to enhance the solubility of hydrophobic drugs in aqueous solutions. This compound can elicit various physiological effects in both vertebrates and invertebrates. Many drugs and drug candidates are hydrophobic, needing solvents like DMSO to be able to reach their physiological targets. As planaria becomes increasingly popular in neuropharmacology research, a description of the DMSO effects in this organism is essential. We found that DMSO is toxic to planarians at concentrations above 5% (705 mM), with an LD(50) of 10% (1.4M) at exposure times above 5 min. At sub-toxic concentrations, DMSO decreases planarian exploratory behavior in a concentration-dependent manner. This reduction in locomotor behavior is reversible and preincubation-independent. DMSO at a concentration of 0.1% (14.1 mM), which is usually enough to solubilize hydrophobic substances in aqueous solutions, did not display any toxic or behavioral effects in planaria. Therefore, in this animal model, DMSO concentrations above 0.1% should be avoided in order to be able to reliably observe any behavioral or toxic effects of hydrophobic drugs.
在这项研究中，我们描述了二甲基亚砜（DMSO）对涡虫的毒性和行为影响。涡虫传统上一直是发育生物学中备受青睐的动物模型。最近，这种生物正被视为神经药理学研究中的动物模型。DMSO常用于细胞和组织培养中作为冷冻保护剂，也常用于提高疏水性药物在水溶液中的溶解度。这种化合物可在脊椎动物和无脊椎动物中引发各种生理效应。许多药物和候选药物都是疏水性的，需要像DMSO这样的溶剂才能到达其生理靶点。随着涡虫在神经药理学研究中越来越受欢迎，描述DMSO对这种生物的影响至关重要。我们发现，DMSO在浓度高于5%（705 mM）时对涡虫有毒，在暴露时间超过5分钟时，其半数致死剂量（LD50）为10%（1.4M）。在亚毒性浓度下，DMSO以浓度依赖的方式降低涡虫的探索行为。这种运动行为的减少是可逆的且与预孵育无关。浓度为0.1%（14.1 mM）的DMSO通常足以使疏水性物质在水溶液中溶解，但在涡虫中未显示出任何毒性或行为影响。因此，在这个动物模型中，应避免使用浓度高于0.1%的DMSO，以便能够可靠地观察疏水性药物的任何行为或毒性影响。
