Respiratory Toxicity of Dimethyl Sulfoxide

Respiratory Toxicity of Dimethyl Sulfoxide
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DOI:
10.1007/5584_2015_187
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发表时间:
2016-01-01
期刊:
影响因子:
6.9
通讯作者:
Okada, Yasumasa
Okada, Yasumasa
中科院分区:
医学2区
文献类型:
--
作者:
Takeda, Kotaro;Pokorski, Mieczyslaw;Okada, Yasumasa

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二甲基亚砜(DMSO)是生物实验中疏水物质最常用的溶剂之一。此外,该化合物具有多种生物活性,这使其具有潜在的药理学用途。DMSO对呼吸的影响,从而对动脉血氧的影响尚不清楚,存在争议,并且是一个研究有限的领域。因此,在本研究中,我们着手确定0.5、1.5、3.5、7.5和15.5 g/kg DMSO累积剂量对肺通气的影响;清醒小鼠每隔1 h腹腔内给予各剂量。在全身体积描记器中记录通气及其对7%缺氧(N-2平衡)的反应。我们证明了DMSO对肺通气及其低氧反应性的剂量依赖性抑制作用,主要由潮汐成分的变化驱动。DMSO对呼吸功能无显著影响的最大安全剂量为3.5 g/kg。7.5 g/kg剂量的DMSO显著抑制呼吸,但对缺氧的过度兴奋反应保持良好。最高剂量15.5 g/kg严重损害通气及其反应。该研究描述了DMSO在呼吸功能方面的安全性,这对于维持适当的组织氧合至关重要。应注意DMSO的剂量浓度。
Dimethyl sulfoxide (DMSO) is one of the most commonly used solvents for hydrophobic substances in biological experiments. In addition, the compound exhibits a plethora of bioactivities, which makes it of potential pharmacological use of its own. The influence on respiration, and thus on arterial blood oxygenation, of DMSO is unclear, contentious, and an area of limited study. Thus, in the present investigation we set out to determine the influence on lung ventilation of cumulated doses of DMSO in the amount of 0.5, 1.5, 3.5, 7.5, and 15.5 g/kg; each dose given intraperitoneally at 1 h interval in conscious mice. Ventilation and its responses to 7 % hypoxia (N-2 balanced) were recorded in a whole body plethsymograph. We demonstrate a dose-dependent inhibitory effect of DMSO on lung ventilation and its hypoxic responsiveness, driven mostly by changes in the tidal component. The maximum safe dose of DMSO devoid of meaningful consequences for respiratory function was 3.5 g/kg. The dose of 7.5 g/kg of DMSO significantly dampened respiration, with yet well preserved hyperventilatory response to hypoxia. The highest dose of 15.5 g/kg severely impaired ventilation and its responses. The study delineates the safety profile of DMSO regarding the respiratory function which is essential for maintaining proper tissue oxygenation. Caution should be exercised concerning dose concentration of DMSO.