In vivo evaluation of novel nitroxyl radicals with reduction stability
| Autor: | Chisato Shirahama, Kiyoshi Sakai, Toshihide Yamasaki, Yuko Ito, Mayumi Yamato, Yuichi Kinoshita, Fumiya Mito, Ken Ichi Yamada, Hisato Deguchi, Hideo Utsumi, Nobuhisa Okukado, Nuttavut Kosem, Kana Kitagawa |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Nitroxide mediated radical polymerization Antioxidant medicine.medical_treatment Contrast Media Blood Pressure Ascorbic Acid Photochemistry medicine.disease_cause Biochemistry Redox Antioxidants Rats Sprague-Dawley Lipid peroxidation Mice chemistry.chemical_compound Drug Stability In vivo Rats Inbred SHR Physiology (medical) medicine Animals Humans Organic chemistry Cells Cultured Mice Inbred ICR Electron Spin Resonance Spectroscopy Nitroxyl Hep G2 Cells Ascorbic acid Rats chemistry Nitrogen Oxides Lipid Peroxidation Oxidation-Reduction Oxidative stress |
| Zdroj: | Free Radical Biology and Medicine. 49:1703-1709 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2010.08.027 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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