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二磷酸二吡啶氧基锰:具有抗氧化和心脏保护特性的磁共振成像造影剂?

Manganese dipyridoxyl diphosphate: MRI contrast agent with antioxidative and cardioprotective properties?

作者信息

Brurok H, Ardenkjaer-Larsen J H, Hansson G, Skarra S, Berg K, Karlsson J O, Laursen I, Jynge P

机构信息

Department of Physiology and Biomedical Engineering, Faculty of Medicine, Norwegian University of Science and Technology, Medisinsk-Teknisk Senter, Trondheim, N-7005, Norway.

出版信息

Biochem Biophys Res Commun. 1999 Jan 27;254(3):768-72. doi: 10.1006/bbrc.1998.0131.

Abstract

Manganese dipyridoxyl diphosphate (MnDPDP) is a contrast agent for magnetic resonance imaging (MRI) of the liver. Aims of the study were to examine if MnDPDP possesses superoxide dismutase (SOD) mimetic activity in vitro, and if antioxidant protection can be demonstrated in an ex vivo rat heart model. Superoxide (*O-2) and hydroxyl radicals (*OH-) were generated in xanthine oxidase and Fenton reactions. Spin adducts with 5,5-dimethyl-1-pyrroline-N-oxide were detected by electron spin resonance spectroscopy. Contractile function and enzyme release were monitored in rat hearts during hypoxia-reoxygenation. Low microM concentrations of MnDPDP and its metabolite Mn dipyridoxyl ethylene-diamine (MnPLED) dismutated *O-2, but showed no activity in Fenton or catalase reactions. MnDPDP 30 microM improved contractile function and reduced enzyme release in rat hearts during reoxygenation. It is concluded that MnDPDP and MnPLED possess SOD mimetic activities and may thereby protect the heart in oxidative stress.

摘要

二磷酸二吡哆醛锰(MnDPDP)是一种用于肝脏磁共振成像(MRI)的造影剂。本研究的目的是检测MnDPDP在体外是否具有超氧化物歧化酶(SOD)模拟活性,以及是否能在离体大鼠心脏模型中证明其抗氧化保护作用。超氧阴离子(*O-2)和羟自由基(OH-)在黄嘌呤氧化酶和芬顿反应中产生。通过电子自旋共振光谱法检测与5,5-二甲基-1-吡咯啉-N-氧化物的自旋加合物。在大鼠心脏缺氧-复氧过程中监测收缩功能和酶释放。低 microM 浓度的 MnDPDP 及其代谢产物二吡哆醛乙二胺锰(MnPLED)可歧化O-2,但在芬顿或过氧化氢酶反应中无活性。30 microM 的 MnDPDP 可改善大鼠心脏复氧过程中的收缩功能并减少酶释放。结论是 MnDPDP 和 MnPLED 具有 SOD 模拟活性,因此可能在氧化应激中保护心脏。

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