Cryoprotectant toxicity neutralization
Cryoprotectant toxicity neutralization
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DOI：
10.1016/j.cryobiol.2009.05.005
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发表时间：
2010-07-01
期刊：
影响因子：
2.7
通讯作者：
Fahy, Gregory M.
中科院分区：
文献类型：
--
作者：
Fahy, Gregory M.
冷冻保护剂毒性是通过冷冻和玻璃化成功冷冻保存生命系统的基本限制因素，并且消除它的能力将是有吸引力的。过去证明“冷冻保护剂毒性中和”（CTN）的尝试经历了许多坎坷。 Baxter 和 Lathe 于 1971 年首次令人信服地提出了某些酰胺可以阻止二甲亚砜 (Me2SO) 毒性作用的概念，这一概念与 1990 年的直接实验相矛盾。但在 1995 年，CTN 的相反模式（Me2SO 阻止甲酰胺的破坏作用）得到了有力证明。最近的实验验证了1995年的原始结果，并将其扩展到尿素和乙酰胺，但没有检测到N-甲基酰胺（N-甲基甲酰胺、N,N-二甲基甲酰胺和N-甲基乙酰胺）的CTN。根据后一种酰胺和乙酰胺可能作为甲酰胺、尿素或Me2SO的低毒性结构类似物的理论，在它们与甲酰胺或尿素之间进行了竞争实验，但这些酰胺-酰胺体系没有观察到CTN。 N-甲基酰胺可能具有非特异性而非特异性毒性的观点得到以下事实的支持：引起毒性的这些酰胺的浓度与使模型蛋白质变性的浓度相似。目前还缺乏中和甘油、丙二醇、乙二醇或 Me2SO 毒性的明确例子，但后者依赖于巯基氧化的影响已被还原剂逆转。综上所述，CTN 是一种有用的现象，具有重要的理论和实践意义。 (C) 2009 Elsevier Inc. 保留所有权利。
Cryoprotectant toxicity is a fundamental limiting factor for the successful cryopreservation of living systems by both freezing and vitrification, and the ability to negate it would be attractive. Past attempts to demonstrate "cryoprotectant toxicity neutralization" (CTN) have had many ups and downs. First convincingly introduced by Baxter and Lathe in 1971, the concept that certain amides can block toxic effects of dimethyl sulfoxide (Me2SO) was contradicted by direct experiments in 1990. But in 1995, the opposite mode of CTN, in which Me2SO blocked the damaging effects of formamide, was robustly demonstrated. Recent experiments have verified the original 1995 results and extended them to urea and acetamide, but no CTN was detected for N-methylamides (N-methylformamide, N,N-dimethylformamide, and N-methylacetamide). On the theory that the latter amides and acetamide might serve as low-toxicity structural analogs of formamide, urea, or Me2SO, competition experiments were carried out between them and formamide or urea, but CTN was not observed for these amide-amide systems. The idea that the N-methylamides might have non-specific rather than specific toxicity was supported by the fact that the concentrations of these amides that cause toxicity are similar to the concentrations that denature model proteins. Clear examples of neutralization of the toxicity of glycerol, propylene glycol, ethylene glycol, or Me2SO are presently lacking, but effects of the latter that depend on sulfhydryl oxidation have been reversed with reducing agents. In summary, CTN is a useful phenomenon with significant theoretical and practical implications. (C) 2009 Elsevier Inc. All rights reserved.