ニトロキシルラジカルと電子スピン共鳴を利用した酸化ストレス関与疾患のメカニズム解析

書誌事項

タイトル別名
  • Mechanistic Analysis of Oxidative Stress-related Diseases Using Nitroxyl Radicals and Electron Spin Resonance

抄録

<p>Excessive production of reactive oxygen species (ROS) causes oxidative stress and is involved in the development and progression of a wide variety of diseases. Therefore, techniques for measuring oxidative stress are indispensable for analysis of the mechanisms of various diseases. The method involving ESR and the durable nitroxyl radical (ESR/spin probe method) is useful for this purpose, because the ESR signal intensity of the spin probe changes on reacting with ROS and other unstable radicals. In this review, the author’s research applying the ESR/spin probe method to clarify disease mechanisms in vivo and in vitro is presented. The ESR signal of the probe injected into animals may decay through a few mechanisms besides reaction with ROS; thus, interpretation of the results is complicated. As the first approach to solving this problem, a probe resistant to enzymatic reduction by introducing a bulky group adjacent to the nitroxy group was created. The second approach was the use of a hydroxylamine probe which dominantly oxidized to nitroxyl radicals by reacting with superoxide anion radicals and oxidants. Using acyl-protected hydroxyl amine, it was demonstrated that sepsis model mice are under oxidative stress due to ROS production by activated phagocytes. On the other hand, it was shown in vitro that the UV-induced radical reaction of ketoprofen also occurs in lipid membranes, and that the reaction is related to ROS generation and membrane disruption. We believe that use of the ESR/spin probe method with ingenuity will clarify the mechanisms of various diseases.</p>

収録刊行物

  • 薬学雑誌

    薬学雑誌 144 (4), 339-344, 2024-04-01

    公益社団法人 日本薬学会

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