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  1. Article: Riboflavin compounds show NAD(P)H dependent quinone oxidoreductase-like quinone reducing activity.

    Nagase, Midori / Sakamoto, Miku / Amekura, Sakiko / Akiba, Sayaka / Kashiba, Misato / Yokoyama, Kenji / Yamamoto, Yorihiro / Fujisawa, Akio

    Journal of clinical biochemistry and nutrition

    2023  Volume 73, Issue 1, Page(s) 52–60

    Abstract: NAD(P)H-dependent quinone oxidoreductase (NQO) is an essential enzyme in living organisms and cells protecting them from oxidative stress. NQO reduces coenzyme Q (CoQ) using NAD(P)H as an electron donor. In the present study, we searched for coenzyme Q10 ...

    Abstract NAD(P)H-dependent quinone oxidoreductase (NQO) is an essential enzyme in living organisms and cells protecting them from oxidative stress. NQO reduces coenzyme Q (CoQ) using NAD(P)H as an electron donor. In the present study, we searched for coenzyme Q10 reducing activity from fractions of gel filtration-fractionated rat liver homogenate. In addition to the large-molecular-weight fraction containing NQO, CoQ10 reducing activity was also detected in a low-molecular-weight fraction. Furthermore, dicumarol, a conventional inhibitor of NQO1 (DT diaphorase), did not inhibit the reduction but quercetin did, suggesting that the activity was not due to NQO1. After further purification, the NADH-dependent CoQ10-reducing compound was identified as riboflavin. Riboflavin is an active substituent of other flavin compounds such as FAD and FMN. These flavin compounds also reduced not only CoQ homologues but also vitamin K homologues in the presence of NADH. The mechanism was speculated to work as follows: NADH reduces flavin compounds to the corresponding reduced forms, and subsequently, the reduced flavin compounds immediately reduce bio-quinones. Furthermore, the flavin-NADH system reduces CoQ10 bound with saposin B, which is believed to function as a CoQ transfer protein
    Language English
    Publishing date 2023-05-16
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 632945-7
    ISSN 1880-5086 ; 0912-0009
    ISSN (online) 1880-5086
    ISSN 0912-0009
    DOI 10.3164/jcbn.22-140
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Simultaneous detection of reduced and oxidized forms of coenzyme Q10 in human cerebral spinal fluid as a potential marker of oxidative stress.

    Nagase, Midori / Yamamoto, Yorihiro / Mitsui, Jun / Tsuji, Shoji

    Journal of clinical biochemistry and nutrition

    2018  Volume 63, Issue 3, Page(s) 205–210

    Abstract: The redox balance of coenzyme Q10 in human plasma is a good marker of oxidative stress because the reduced form of coenzyme Q10 (ubiquinol-10) is very sensitive to oxidation and is quantitatively converted to its oxidized form (ubiquinone-10). Here we ... ...

    Abstract The redox balance of coenzyme Q10 in human plasma is a good marker of oxidative stress because the reduced form of coenzyme Q10 (ubiquinol-10) is very sensitive to oxidation and is quantitatively converted to its oxidized form (ubiquinone-10). Here we describe an HPLC method for simultaneous detection of ubiquinol-10 and ubiquinone-10 in human cerebral spinal fluid to meet a recent demand for measuring local oxidative stress. Since the levels of coenzyme Q10 in human cerebral spinal fluid are less than 1/500 of those in human plasma, cerebral spinal fluid extracted with 2-propanol requires concentration for electrochemical detection. Using human plasma diluted 500-fold with physiological saline as a pseudo-cerebral spinal fluid, we found that addition of
    Language English
    Publishing date 2018-06-08
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 632945-7
    ISSN 1880-5086 ; 0912-0009
    ISSN (online) 1880-5086
    ISSN 0912-0009
    DOI 10.3164/jcbn.17-131
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Increased oxidative stress and coenzyme Q10 deficiency in centenarians.

    Nagase, Midori / Yamamoto, Yorihiro / Matsumoto, Nozomi / Arai, Yasumichi / Hirose, Nobuyoshi

    Journal of clinical biochemistry and nutrition

    2018  Volume 63, Issue 2, Page(s) 129–136

    Abstract: Aging populations are expanding worldwide, and the increasing requirement for nursing care has become a serious problem. Furthermore, successful aging is one of the highest priorities for individuals and societies. Centenarians are an informative cohort ... ...

    Abstract Aging populations are expanding worldwide, and the increasing requirement for nursing care has become a serious problem. Furthermore, successful aging is one of the highest priorities for individuals and societies. Centenarians are an informative cohort to study and inflammation has been found to be a key factor in predicting cognition and physical capabilities. Inflammation scores have been determined based on the levels of cytokines and C-reactive protein, however, serum antioxidants and lipid profiles have not been carefully examined. We found that the redox balance of coenzyme Q10 significantly shifted to the oxidized form and levels of strong antioxidants, such as ascorbic acid and unconjugated bilirubin, decreased significantly compared to 76-year-old controls, indicating an increased oxidative stress in centenarians. Levels of uric acid, an endogenous peroxynitrite scavenger, remained unchanged, suggesting that centenarians were experiencing moderate, chronic inflammatory conditions. Centenarians exhibited a hypocholesterolemic condition, while an increase in the ratio of free cholesterol to cholesterol esters suggests some impairment of liver function. Serum free fatty acids and monoenoic acid composition, markers of tissue oxidative damage, were significantly decreased in centenarians, indicating an impairment in the tissue repair system. Despite an elevation of the coenzyme Q10 binding protein Psap, serum total coenzyme Q10 levels decreased in centenarians. This suggests a serious deficiency of coenzyme Q10 in tissues, since tissue levels of coenzyme Q10 significantly decrease with age. Therefore, coenzyme Q10 supplementation could be beneficial for centenarians.
    Language English
    Publishing date 2018-03-17
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 632945-7
    ISSN 1880-5086 ; 0912-0009
    ISSN (online) 1880-5086
    ISSN 0912-0009
    DOI 10.3164/jcbn.17-124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration.

    Nagase, Midori / Yamamoto, Yorihiro / Miyazaki, Yusuke / Yoshino, Hiide

    Redox report : communications in free radical research

    2016  Volume 21, Issue 3, Page(s) 104–112

    Abstract: Objectives and methods: Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) ...

    Abstract Objectives and methods: Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined.
    Results and discussion: Among 26 ALS patients, 17 received edaravone (30 mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n = 19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (ΔALSFRS-R ≥ 0) as compared to the ingravescent group (ΔALSFRS-R < -5). Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease %CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.
    MeSH term(s) Aged ; Amyotrophic Lateral Sclerosis/drug therapy ; Amyotrophic Lateral Sclerosis/metabolism ; Antipyrine/analogs & derivatives ; Antipyrine/therapeutic use ; Biomarkers/blood ; Edaravone ; Fatty Acids, Nonesterified/blood ; Female ; Free Radical Scavengers/therapeutic use ; Humans ; Male ; Middle Aged ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Peroxynitrous Acid/blood ; Ubiquinone/analogs & derivatives ; Ubiquinone/blood ; Uric Acid/blood
    Chemical Substances Biomarkers ; Fatty Acids, Nonesterified ; Free Radical Scavengers ; Ubiquinone (1339-63-5) ; Peroxynitrous Acid (14691-52-2) ; Uric Acid (268B43MJ25) ; coenzyme Q10 (EJ27X76M46) ; Edaravone (S798V6YJRP) ; Antipyrine (T3CHA1B51H)
    Language English
    Publishing date 2016-02-25
    Publishing country England
    Document type Clinical Trial ; Journal Article
    ZDB-ID 1305290-1
    ISSN 1743-2928 ; 1351-0002
    ISSN (online) 1743-2928
    ISSN 1351-0002
    DOI 10.1179/1351000215Y.0000000026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4584: Show issues Location:
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  5. Article: Increased oxidative stress and renal injury in patients with sepsis.

    Yamaguchi, Junko / Nagase, Midori / Yamamoto, Yorihiro / Sakurai, Atsushi / Kubo, Airi / Mitsuhashi, Hikaru / Matsuoka, Masaru / Ihara, Shingo / Kinoshita, Kosaku

    Journal of clinical biochemistry and nutrition

    2018  Volume 63, Issue 2, Page(s) 137–143

    Abstract: Sepsis remains one of the leading causes of death in intensive care units. The early phase of sepsis is characterized by a massive formation of reactive oxygen and nitrogen species such as superoxide and nitric oxide. However, few comprehensive studies ... ...

    Abstract Sepsis remains one of the leading causes of death in intensive care units. The early phase of sepsis is characterized by a massive formation of reactive oxygen and nitrogen species such as superoxide and nitric oxide. However, few comprehensive studies on plasma antioxidants have been reported. Increased oxidative stress was confirmed in sepsis patients (
    Language English
    Publishing date 2018-03-17
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 632945-7
    ISSN 1880-5086 ; 0912-0009
    ISSN (online) 1880-5086
    ISSN 0912-0009
    DOI 10.3164/jcbn.17-130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Oxidative stress and abnormal cholesterol metabolism in patients with post-cardiac arrest syndrome.

    Nagase, Midori / Sakurai, Atsushi / Sugita, Atsunori / Matsumoto, Nozomi / Kubo, Airi / Miyazaki, Yusuke / Kinoshita, Kosaku / Yamamoto, Yorihiro

    Journal of clinical biochemistry and nutrition

    2017  Volume 61, Issue 2, Page(s) 108–117

    Abstract: Patients with post-cardiac arrest syndrome (PCAS) suffer from whole body ischemia/reperfusion injury similar to that experienced by newborn babies. Increased oxidative stress was confirmed in PCAS patients ( ...

    Abstract Patients with post-cardiac arrest syndrome (PCAS) suffer from whole body ischemia/reperfusion injury similar to that experienced by newborn babies. Increased oxidative stress was confirmed in PCAS patients (
    Language English
    Publishing date 2017-07-28
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 632945-7
    ISSN 1880-5086 ; 0912-0009
    ISSN (online) 1880-5086
    ISSN 0912-0009
    DOI 10.3164/jcbn.17-30
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Randomized, double-blind, placebo-controlled pilot trial of reduced coenzyme Q10 for Parkinson's disease.

    Yoritaka, Asako / Kawajiri, Sumihiro / Yamamoto, Yorihiro / Nakahara, Toshiki / Ando, Maya / Hashimoto, Kazuhiko / Nagase, Midori / Saito, Yufuko / Hattori, Nobutaka

    Parkinsonism & related disorders

    2015  Volume 21, Issue 8, Page(s) 911–916

    Abstract: Introduction: Mitochondrial complex I deficiencies have been found in post-mortem brains of patients with Parkinson's disease (PD). Coenzyme Q10 (CoQ10) is the electron acceptor found in complexes I and II, and is a potent antioxidant. A recent trial of ...

    Abstract Introduction: Mitochondrial complex I deficiencies have been found in post-mortem brains of patients with Parkinson's disease (PD). Coenzyme Q10 (CoQ10) is the electron acceptor found in complexes I and II, and is a potent antioxidant. A recent trial of the oxidized form of CoQ10 for PD failed to show benefits; however, the reduced form of CoQ10 (ubiquinol-10) has shown better neuroprotective effects in animal models.
    Methods: Randomized, double-blind, placebo-controlled, parallel-group pilot trials were conducted to assess the efficacy of ubiquinol-10 in Japanese patients with PD. Participants were divided into two groups: PD experiencing wearing off (Group A), and early PD, without levodopa (with or without a dopamine agonist) (Group B). Participants took 300 mg of ubiquinol-10 or placebo per day for 48 weeks (Group A) or 96 weeks (Group B).
    Results: In Group A, total Unified Parkinson's Disease Rating Scale (UPDRS) scores decreased in the ubiquinol-10 group (n = 14; mean ± SD [-4.2 ± 8.2]), indicating improvement in symptoms. There was a statistically significant difference (p < 0.05) compared with the placebo group (n = 12; 2.9 ± 8.9). In Group B, UPDRS increased in the ubiquinol-10 group (n = 14; 3.9 ± 8.0), as well as in the placebo group (n = 8; 5.1 ± 10.3).
    Conclusions: This is the first report showing that ubiquinol-10 may significantly improve PD with wearing off, as judged by total UPDRS scores, and that ubiquinol-10 is safe and well tolerated.
    MeSH term(s) Aged ; Antioxidants/administration & dosage ; Antioxidants/pharmacology ; Double-Blind Method ; Female ; Humans ; Male ; Middle Aged ; Neuroprotective Agents/administration & dosage ; Neuroprotective Agents/pharmacology ; Parkinson Disease/drug therapy ; Pilot Projects ; Treatment Outcome ; Ubiquinone/administration & dosage ; Ubiquinone/analogs & derivatives ; Ubiquinone/pharmacology
    Chemical Substances Antioxidants ; Neuroprotective Agents ; Ubiquinone (1339-63-5) ; coenzyme Q10 (EJ27X76M46) ; ubiquinol (M9NL0C577Y)
    Language English
    Publishing date 2015-08
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 1311489-x
    ISSN 1873-5126 ; 1353-8020
    ISSN (online) 1873-5126
    ISSN 1353-8020
    DOI 10.1016/j.parkreldis.2015.05.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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