In vivo evaluation of novel nitroxyl radicals with reduction stability

Yuichi Kinoshita, Ken-Ichi Yamada, Toshihide Yamasaki, Fumiya Mito, Mayumi Yamato, Nuttavut Kosem, Hisato Deguchi, Chisato Shirahama, Yuko Ito, Kana Kitagawa, Nobuhisa Okukado, Kiyoshi Sakai, Hideo Utsumi

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Nitroxyl radicals (nitroxide) have great potential advantages as spin probes, antioxidants, contrast agents, and radiation-protecting agents. However, they are readily reduced by reductants in cells and lose their paramagnetic nature. Recently, tetraethyl-substituted nitroxyl radicals have been reported to have high stability toward reduction by ascorbic acid (AsA). We report the general considerations of tetraethyl nitroxyl radicals for in vivo application. The reason for the low reactivity to AsA reduction was the positive value of Gibbs energy between the tetraethyl nitroxyl radical and AsA. Further, these compounds had an inhibitory effect on lipid peroxidation despite having AsA resistance. They had low antiproliferative effects in HepG2 cells and HUVECs and did not have a lowering effect on blood pressure in animals. Further, after intravenous injection, the ESR signal intensities of tetraethyl-substituted piperidine nitroxyl radicals were very stable in mice over 20 min. These results suggest that tetraethyl-substituted nitroxyl radicals have stability against bioreduction with reductants such as AsA and confer onto them features as antioxidants and paramagnetic tracers/contrast agents. Hence, they will be useful in identifying the foci of oxidative stress in vivo using redox-based imaging approaches.

Original languageEnglish
Pages (from-to)1703-1709
Number of pages7
JournalFree Radical Biology and Medicine
Volume49
Issue number11
DOIs
Publication statusPublished - Dec 1 2010

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Ascorbic Acid
Reducing Agents
Contrast Media
Antioxidants
Acid resistance
Oxidative stress
Blood pressure
Hep G2 Cells
Gibbs free energy
nitroxyl
Intravenous Injections
Lipid Peroxidation
Oxidation-Reduction
Paramagnetic resonance
Animals
Oxidative Stress
Radiation
Blood Pressure
Lipids
Imaging techniques

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

In vivo evaluation of novel nitroxyl radicals with reduction stability. / Kinoshita, Yuichi; Yamada, Ken-Ichi; Yamasaki, Toshihide; Mito, Fumiya; Yamato, Mayumi; Kosem, Nuttavut; Deguchi, Hisato; Shirahama, Chisato; Ito, Yuko; Kitagawa, Kana; Okukado, Nobuhisa; Sakai, Kiyoshi; Utsumi, Hideo.

In: Free Radical Biology and Medicine, Vol. 49, No. 11, 01.12.2010, p. 1703-1709.

Research output: Contribution to journalArticle

Kinoshita, Y, Yamada, K-I, Yamasaki, T, Mito, F, Yamato, M, Kosem, N, Deguchi, H, Shirahama, C, Ito, Y, Kitagawa, K, Okukado, N, Sakai, K & Utsumi, H 2010, 'In vivo evaluation of novel nitroxyl radicals with reduction stability', Free Radical Biology and Medicine, vol. 49, no. 11, pp. 1703-1709. https://doi.org/10.1016/j.freeradbiomed.2010.08.027
Kinoshita, Yuichi ; Yamada, Ken-Ichi ; Yamasaki, Toshihide ; Mito, Fumiya ; Yamato, Mayumi ; Kosem, Nuttavut ; Deguchi, Hisato ; Shirahama, Chisato ; Ito, Yuko ; Kitagawa, Kana ; Okukado, Nobuhisa ; Sakai, Kiyoshi ; Utsumi, Hideo. / In vivo evaluation of novel nitroxyl radicals with reduction stability. In: Free Radical Biology and Medicine. 2010 ; Vol. 49, No. 11. pp. 1703-1709.
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