YAKUGAKU ZASSHI

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Volume 144 (2024) Issue 4 Pages 339-344

Mechanistic Analysis of Oxidative Stress-related Diseases Using Nitroxyl Radicals and Electron Spin Resonance

Shoko Okazaki

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.

Editor's pick

Nitroxyl radicals are used as probes for ROS measurement by ESR. Therefore, it is important to select appropriate probes and modifications for the evaluation of the relationship between oxidative stress and various diseases. This review introduces a study on the pharmacokinetics of probes, in vivo redox evaluation of sepsis model mice using acyl-protected probes, and an examination of the photosensitivity mechanism.

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2024 Volume 144 Issue 4

What is the Initiating Reaction for the Lipid Radical Chain Reaction System That Can Induce Ferroptotic Cell Death at the Lower Oxygen Content? Ichiro Koshiishi
Evaluation of the Simple Suspension Method for Oral Anticancer Drugs Tomoya Abe, Sanae Kusakabe, Miho Naoi, Takayuki Suzuki, Atsunobu Sagara, Makoto Hiraide, Motohiko Sano, Toshiaki Nakayama
Exploration of Risk Factors of the Onset of Antibiotics-induced Acute Kidney Injury and Its Transfer to Chronic Kidney Disease Using the Medical Information Database Masaya Ieda, Yuka Kuroda, Takahiro Matsumoto, Ayaka Yamashita, Takashi Watanabe, Katsuhito Hori, Michio Kimura, Junichi Kawakami, Masahiro Tohkin
Examination of Analytical Method for Tris(2,3-dibromopropyl)phosphate and Bis(2,3-dibromopropyl)phosphate to Revise the Official Methods Based on “Act on the Control of Household Products Containing Harmful Substances” Tsuyoshi Kawakami, Tomoko Ooshima, Masayuki Ohyama, Naeko Sugaya, Iwaki Nishi, Taichi Yoshitomi, Hisayoshi Takai, Takanari Wakayama, Hiroyuki Ohno, Maiko Tahara, Yoshiaki Ikarashi

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