Evaluation of DEPMPO as a spin trapping agent in biological systems
Evaluation of DEPMPO as a spin trapping agent in biological systems
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DOI：
10.1016/s0891-5849(98)00251-2
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发表时间：
1999-03-01
影响因子：
7.4
通讯作者：
Swartz, H
中科院分区：
文献类型：
--
作者：
Liu, KJ;Miyake, M;Swartz, H
研究了自旋捕捉剂5-diethoxyphosphoryl-5-methyl-1-pyrroline-n-oxide的细胞毒性、药代动力学、体内外稳定性，并与广泛使用的自旋捕捉剂5，5-二甲基-1-吡咯啉-N-氧化物进行了比较。与DMPO相似，DEPMPO在腹腔注射后迅速被吸收，并均匀分布于小鼠的肝脏、心脏和血液中。在抗坏血酸存在下，DEPMPO/SO3加合物的体外稳定性是DMPO/SO3的7倍。在体内条件下，自旋加合物DEPMPO/SO3.-的稳定性是DMPO/SO3的2-4倍，这取决于加合物的给药途径。利用低频EPR光谱仪，我们能够直接观察到DMPO和DEPMPO在正常小鼠体内的自旋俘获SO3·-自由基。DEPMPO在低至1 mM的浓度下具有可检测到的自旋加合信号，而DMPO的浓度为5 mM。我们得出的结论是，DEPMPO是一种潜在的在功能生物系统中捕获自由基的很好的候选者，并且代表着对常用的陷阱DMPO的改进。(C)1999年爱思唯尔科学公司。
Cellular toxicity, pharmacokinetics, and the in vitro and in vivo stability of the SO3.- spin adduct of the spin trap, 5-diethoxyphosphoryl-5-methyl-1-pyrroline-n-oxide (DEPMPO), was investigated, and the results were compared with those of the widely used spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Similar to DMPO, DEPMPO was quickly taken up (< 15 min) after intraperitoneal injection, and distributed evenly in the liver, heart, and blood of the mice. In the presence of ascorbate the in vitro stability of the adduct DEPMPO/SO3.- was 7 times better than DMPO/SO3.-. Under in vivo conditions, the spin adduct DEPMPO/SO3.- was 2-4 times more stable than DMPO/ SO3.-, depending on the route of administration of the adducts. Using a low frequency EPR spectrometer, we were able to observe the spin trapped SO3.- radical both with DMPO and DEPMPO directly in the intact mouse. DEPMPO had a detectable spin adduct signal at a concentration as low as 1 mM, as compared to 5 mM for DMPO. We conclude that DEPMPO is potentially a good candidate for trapping radicals in functioning biological systems, and represents an improvement over the commonly used trap DMPO. (C) 1999 Elsevier Science Inc.