Fuminori Hyodo

Kyushu University, Hukuoka, Fukuoka, Japan

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Publications (49)190.69 Total impact

  • Fuminori Hyodo · Shinji Ito · Hideo Utsumi
    YAKUGAKU ZASSHI 01/2015; 135(5):725-31. DOI:10.1248/yakushi.14-00235-2 · 0.31 Impact Factor
  • YAKUGAKU ZASSHI 01/2015; 135(5):739-43. DOI:10.1248/yakushi.14-00235-4 · 0.31 Impact Factor
  • Kazunori Anzai · Fuminori Hyodo
    YAKUGAKU ZASSHI 01/2015; 135(5):717-8. DOI:10.1248/yakushi.14-00235-F · 0.31 Impact Factor
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    ABSTRACT: Redox reactions that generate free radical intermediates are essential to metabolic processes. However, their intermediates can produce reactive oxygen species, which may promote diseases related to oxidative stress. We report here the use of dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) to conduct redox molecular imaging. Using DNP-MRI, we obtained simultaneous images of free radical intermediates generated from the CoQ10, FMN, and FAD involved in the mitochondrial electron transport chain, as well as the radicals derived from vitamins E and K1. Each of these free radicals was imaged in real time in a phantom comprising a mixture of free radicals localized in either lipophilic or aqueous environments. Changing the frequency of electron spin resonance (ESR) irradiation also allowed each of the radical species to be distinguished in the spectroscopic images. This study is the first to report the spectroscopic DNP-MRI imaging of free radical intermediates that are derived from endogenous species involved in metabolic processes.
    Analytical Chemistry 07/2014; 86(15). DOI:10.1021/ac502150x · 5.83 Impact Factor
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    ABSTRACT: Electron spin resonance (ESR) studies were carried out for 2mM 14N labeled deutrated permeable 3- methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) in pure water, 1 mM, 2 mM, 3 mM and 4 mM concentration of MC-PROXYL in 300 mM concentration of liposomal solution by using a L-band ESR spectrometer. The ESR parameters such as linewidth, hyperfine coupling constant, g-factor, partition parameter and permeability were reported. The partition parameter and permeability values indicate the maximum spin distribution in the lipid phase at 2 mM concentration. This study illustrates that ESR can be used to differentiate between the intra and extra-membrane water by loading the liposome vesicles with a lipid-permeable nitroxyl spin probe. From the ESR results, the radical concentration was optimized as 2 mM in liposomal solution for ESR phantom studies and experiments.
    03/2014; 1591(1). DOI:10.1063/1.4872551
  • Fuminori Hyodo · Shinji Ito · Hideo Utsumi
    Bunseki kagaku 01/2014; 63(6):467-476. DOI:10.2116/bunsekikagaku.63.467 · 0.22 Impact Factor
  • Free Radical Biology and Medicine 11/2013; 65:S126. DOI:10.1016/j.freeradbiomed.2013.10.707 · 5.71 Impact Factor
  • Free Radical Biology and Medicine 11/2013; 65:S126. DOI:10.1016/j.freeradbiomed.2013.10.708 · 5.71 Impact Factor
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    ABSTRACT: Cyclic nitroxides are a diverse group of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15–20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described, including their ability to degrade superoxide and peroxide, inhibit Fenton reactions, and undergo radical–radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use, including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. Although much remains to be done, many applications have been well studied and some are currently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials.
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    ABSTRACT: Electron spin resonance (ESR) studies were carried out for 2mM 14N-labeled deutrated 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) and 3-carboxy-2,2,5,5,-tetramethyl-1-pyrrolidinyloxy (carboxy-PROXYL) in pure water and various concentrations of liposomal solutions by using 300 MHz ESR spectrometer. The ESR parameters such as the line width, hyperfine coupling constant, g-factor, rotational correlation time, partition parameter and permeability were reported for the samples. The permeable and impermeable nature of nitroxyl spin probes was demonstrated. The increased rotational correlation time was observed for MC-PROXYL, which indicates the permeable and less mobile nature of the nitroxyl spin probe. The obtained partition parameter and permeability values are used to quantify the permeable nature of the nitroxyl spin probe. The peaks correspond to lipid phase were observed for MC-PROXYL in liposomal solution, but that peak was not observed for carboxy-PROXYL. These results indicate the permeable and the impermeable nature of nitroxyl spin probes.
    02/2013; DOI:10.1063/1.4790946
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    ABSTRACT: The recent development of a bi-modality magnetic resonance imaging/electron paramagnetic resonance imaging (MRI/EPRI) platform has enabled longitudinal monitoring of both tumor oxygenation and redox status in murine cancer models. The current study used this imaging platform to test the hypothesis that a more reducing tumor microenvironment accompanies the development of tumor hypoxia. To test this, the redox status of the tumor was measured using Tempol as a redox‑sensitive MRI contrast agent, and tumor hypoxia was measured with Oxo63, which is an oxygen-sensitive EPRI spin probe. Images were acquired every 1-2 days in mice bearing SCCVII tumors. The median pO2 decreased from 14 mmHg at 7 days after tumor implantation to 7 mmHg at 15 days after implantation. Additionally, the hypoxic fraction, defined as the percentage of the tumor that exhibited a pO2<10 mmHg, increased with tumor size (from 10% at 500 mm3 to 60% at 3,500 mm3). The rate of Tempol reduction increased as a function of tumor volume (0.4 min-1 at 500 mm3 to 1.7 min-1 at 3,500 mm3), suggesting that the tumor microenvironment became more reduced as the tumor grew. The results show that rapid Tempol reduction correlates with decreased tumor oxygenation, and that the Tempol decay rate constant may be a surrogate marker for tumor hypoxia.
    International Journal of Oncology 09/2012; 41(6). DOI:10.3892/ijo.2012.1638 · 3.03 Impact Factor
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    ABSTRACT: Electron spin resonance studies were carried out for 2mM 14N labeled 2H enriched 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) in pure water and 100, 200, 300, 400 mM concentrations of liposomal solution and 3-carboxy-2,2,5,5,-tetramethyl-1-pyrrolidinyloxy (carboxy-PROXYL) in pure water and 400 mM concentration of liposomal solution by using L-band ESR spectrometer. This study reveals that the permeability of MC-PROXYL in liposomal solution and impermeability of carboxy-PROXYL in 400 mM concentration of liposomal solution. This study illustrates that the ESR can be used to differentiate between the intra-and extra-membrane water by loading the liposome vesicles with a lipid permeable nitroxyl spin probe. The lipid membrane permeability of two different nitroxyl spin probes was demonstrated.
    06/2012; 44(4):185-186. DOI:10.1063/1.4709942
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    ABSTRACT: Overhauser-enhanced MRI (OMRI) enables visualization of free radicals in animals based on dynamic nuclear polarization. Real-time data of tissue redox status gathered from kinetic images of redox-sensitive nitroxyl radical probes using OMRI provided both anatomic and physiological information. Phantom experiments demonstrated the linear correlation between the enhancement factor and the concentration of a membrane-impermeable probe, carboxy-PROXYL (3-carboxy-2,2,5,5-tetramethyl- pyrrolidine-1-oxyl). Whole-body OMRI images illustrated the in vivo kinetics of carboxy-PROXYL for 25 min. Initial distribution was observed in lung, heart, liver, and kidney, but not brain, corresponding to its minimal lipophilicity. Based on these images (pixel size, 1.33 × 1.33 mm; slice thickness, 50mm), a time-concentration curve with low coefficient of variance (<0.21) was created to assess pharmacokinetic behaviors. A biexponential curve showed a distribution phase from 1 to 10 min and an elimination phase from 15 to 25 min. The α rate constant was greater than the β rate constant in ROIs, confirming that its pharmacokinetics obeyed a two-compartment model. As a noninvasive technique, combining OMRI imaging with redox probes to monitor tissue redox status may be useful in acquiring valuable information regarding organ function for preclinical and clinical studies of oxidative diseases.
    Free Radical Biology and Medicine 04/2012; 53(2):328-36. DOI:10.1016/j.freeradbiomed.2012.04.026 · 5.71 Impact Factor
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    ABSTRACT: Electron paramagnetic resonance (EPR) oximetry at 700 MHz operating frequency employing a surface coil resonator is used to assess tissue partial pressure of oxygen (pO(2)) using paramagnetic media whose linewidth and decay constant are related to oxygen concentration. Differences in extracellular and intracellular pO(2) in squamous cell carcinoma (SCC) tumor tissue were tested using several types of water-soluble paramagnetic media, which localize extracellularly or permeate through the cell membrane. The nitroxide carboxy-PROXYL (CxP) can only be distributed in blood plasma and extracellular fluids whereas the nitroxides carbamoyl-PROXYL (CmP) and TEMPOL (TPL) can permeate cell membranes and localize intracellularly. EPR signal decay constant and the linewidth of the intravenously administered nitroxides in SCC tumor tissues implanted in mouse thigh and the contralateral normal muscle of healthy mice breathing gases with different pO(2) were compared. The pO(2) in the blood can depend on the oxygen content in the breathing gas while tissue pO(2) was not directly influenced by pO(2) in the breathing gas. The decay constants of CmP and TPL in tumor tissue were significantly larger than in the normal muscles, and lower linewidths of CmP and TPL in tumor tissue was observed. The SCC tumor showed intracellular hypoxia even though the extracellular pO(2) is similar to normal tissue in the peripheral region.
    Biological & Pharmaceutical Bulletin 01/2011; 34(1):142-5. DOI:10.1248/bpb.34.142 · 1.78 Impact Factor
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    ABSTRACT: Nitroxyl contrast agents (nitroxyl radicals, also known as nitroxide) are paramagnetic species, which can react with reactive oxygen species (ROS) to lose paramagnetism to be diamagnetic species. The paramagnetic nitroxyl radical forms can be detected by using electron paramagnetic resonance imaging (EPRI), Overhauser MRI (OMRI), or MRI. The time course of in vivo image intensity induced by paramagnetic redox-sensitive contrast agent can give tissue redox information, which is the so-called redox imaging technique. The redox imaging technique employing a blood-brain barrier permeable nitroxyl contrast agent can be applied to analyze the pathophysiological functions in the brain. A brief theory of redox imaging techniques is described, and applications of redox imaging techniques to brain are introduced.
    Methods in molecular biology (Clifton, N.J.) 01/2011; 711:397-419. DOI:10.1007/978-1-61737-992-5_20 · 1.29 Impact Factor
  • Free Radical Biology and Medicine 12/2010; 49. DOI:10.1016/j.freeradbiomed.2010.10.527 · 5.71 Impact Factor
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    ABSTRACT: A sensitive and simultaneous analytical technique for visualizing multiple endogenous molecules is now strongly required in biological science. Here, we show the applicability of a matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) system for getting chemically diverse metabolite profiles on a single-mammalian cell. This ultrahighly sensitive MALDI-MS technique enabled a spatially resolved detection of a broad range of metabolites including nucleotides, cofactors, phosphorylated sugars, amino acids, lipids, and carboxylic acids in normal mouse brain tissue with their unique distributions. Furthermore, a combination of MS imaging and metabolic pathway analysis of a rat transient middle cerebral artery occlusion model visualized a spatiotemporal behavior of metabolites in the central metabolic pathway regulated by an ischemia reperfusion. These findings highlight potential applications of an in situ metabolomic imaging technique to visualize spatiotemporal dynamics of the tissue metabolome, which will facilitate biological discovery in both preclinical and clinical settings.
    Analytical Chemistry 11/2010; 82(23):9789-96. DOI:10.1021/ac101998z · 5.83 Impact Factor
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    ABSTRACT: Radiation is used in the treatment of a broad range of malignancies. Exposure of normal tissue to radiation may result in both acute and chronic toxicities that can result in an inability to deliver the intended therapy, a range of symptoms, and a decrease in quality of life. Radioprotectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. Herein, we review agents in clinical use or in development as radioprotectors and mitigators of radiation-induced normal tissue injury. Few agents are approved for clinical use, but many new compounds show promising results in preclinical testing.
    The Oncologist 04/2010; 15(4):360-71. DOI:10.1634/theoncologist.2009-S104 · 4.54 Impact Factor
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    ABSTRACT: Geldanamycin (GM), a benzoquinone ansamycin antibiotic, is a natural product inhibitor of Hsp90 with potent and broad anti-cancer properties. Because of its adverse effects on liver, its less toxic derivatives 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) and 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) are currently being evaluated for the treatment of cancer. Previously, it has been demonstrated that the redox cycling of GM by NADPH-cytochrome P450 reductase leads to the formation of the GM semiquinone and superoxide radicals, the latter being identified using spin-trapping. We hypothesized that the different hepatotoxicity induced by GM, 17-AAG and 17-DMAG reflects the redox active properties of the quinone moiety and possibly the extent of superoxide formation, which may stimulate cellular oxidative injury. Our data demonstrate that superoxide can be efficiently trapped during the reduction of GM, 17-AAG and 17-DMAG by NADPH-cytochrome P450 reductase, and that superoxide formation rate followed the order 17-DMAG > 17-AAG > GM. In the absence of superoxide scavengers, the rate of NADPH oxidation followed the order 17-DMAG > GM > 17-AAG. The half-wave one-electron reduction potentials (E(1/2)) of GM, 17-AAG and 17-DMAG in DMSO have been determined to be -0.37, -0.13 and -0.015V (vs. Ag/AgCl), respectively. If the same order of E(1/2) follows in neutral aqueous media, thermodynamic considerations imply that 17-DMAG is more readily reduced by the P450 reductase as well as by superoxide. The order of the drug cytotoxicity toward rat primary hepatocytes, as determined by their effect on cell viability and on intracellular oxidant level, was opposite to the order of E(1/2) of the respective quinone/semiquinone couples. These results suggest that hepatotoxicity exhibited by the Hsp90 inhibitors belonging to benzoquinone ansamycins could be attributed to superoxide. The apparent discrepancy between the order of toxicity and the orders of superoxide formation rate, which is correlated with E(1/2), is discussed.
    Free Radical Biology and Medicine 03/2010; 48(11):1559-63. DOI:10.1016/j.freeradbiomed.2010.03.001 · 5.71 Impact Factor

Publication Stats

1k Citations
190.69 Total Impact Points


  • 2004–2014
    • Kyushu University
      • • Innovation Center for Medical Redox Navigation
      • • Graduate School of Pharmaceutical Sciences
      • • Faculty of Pharmaceutical Sciences
      Hukuoka, Fukuoka, Japan
  • 2006–2013
    • National Cancer Institute (USA)
      • • Radiation Biology Branch
      • • Center for Cancer Research
      Maryland, United States
  • 2012
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 2011
    • National Institute of Radiological Sciences
      • Research Center for Charged Particle Therapy
      Chiba-shi, Chiba-ken, Japan
  • 2010
    • Doshisha University
      Kioto, Kyōto, Japan
  • 2007–2010
    • National Institutes of Health
      • Branch of Radiation Biology
      Bethesda, MD, United States
  • 2008
    • Washington University in St. Louis
      • Department of Biochemistry and Molecular Biophysics
      San Luis, Missouri, United States