Confirmation of superoxide generation via xanthine oxidase in streptozotocin-induced diabetic mice

Shingo Matsumoto, Ichiro Koshiishi, Toyoshi Inoguchi, Hajime Nawata, Hideo Utsumi

    Research output: Contribution to journalArticle

    87 Citations (Scopus)

    Abstract

    Reactive oxygen species (ROS) may play key roles in vascular inflammation and atherogenesis in patients with diabetes. In this study, xanthine oxidase (XO) system was examined as a potential source of superoxide in mice with streptozotocin (STZ)-induced experimental diabetes. Plasma XO activity increased 3-fold in diabetic mice (50 ± 33 μU/ml) 2 weeks after the onset of diabetes, as compared with non-diabetic control mice (15 ± 6 μU/ml). In vivo superoxide generation in diabetic mice was evaluated by an in vivo electron spin resonance (ESR)/spin probe method. Superoxide generation was significantly enhanced in diabetic mice, and the enhancement was restored by the administration of superoxide dismutase (SOD) and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron), which was reported to scavenge superoxide. Pretreatment of diabetic mice with XO inhibitors, allopurinol and its active metabolite oxipurinol, normalized the increased superoxide generation. In addition, there was a correlation (r = 0.78) between the level of plasma XO activity and the relative degree of superoxide generation in diabetic and non-diabetic mice. Hence, the results of this study strongly suggest that superoxide should be generated through the increased XO seen in the diabetic model mice, which may be involved in the pathogenesis of diabetic vascular complications.

    Original languageEnglish
    Pages (from-to)767-772
    Number of pages6
    JournalFree Radical Research
    Volume37
    Issue number7
    DOIs
    Publication statusPublished - Jul 1 2003

    Fingerprint

    Xanthine Oxidase
    Streptozocin
    Superoxides
    Medical problems
    Oxypurinol
    1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt
    Plasmas
    Allopurinol
    Diabetic Angiopathies
    Metabolites
    Benzene
    Electron Spin Resonance Spectroscopy
    Superoxide Dismutase
    Paramagnetic resonance
    Reactive Oxygen Species
    Blood Vessels
    Atherosclerosis
    Acids
    Inflammation

    All Science Journal Classification (ASJC) codes

    • Biochemistry

    Cite this

    Confirmation of superoxide generation via xanthine oxidase in streptozotocin-induced diabetic mice. / Matsumoto, Shingo; Koshiishi, Ichiro; Inoguchi, Toyoshi; Nawata, Hajime; Utsumi, Hideo.

    In: Free Radical Research, Vol. 37, No. 7, 01.07.2003, p. 767-772.

    Research output: Contribution to journalArticle

    Matsumoto, Shingo ; Koshiishi, Ichiro ; Inoguchi, Toyoshi ; Nawata, Hajime ; Utsumi, Hideo. / Confirmation of superoxide generation via xanthine oxidase in streptozotocin-induced diabetic mice. In: Free Radical Research. 2003 ; Vol. 37, No. 7. pp. 767-772.
    @article{74f16b02e3234e0087144788322b8c94,
    title = "Confirmation of superoxide generation via xanthine oxidase in streptozotocin-induced diabetic mice",
    abstract = "Reactive oxygen species (ROS) may play key roles in vascular inflammation and atherogenesis in patients with diabetes. In this study, xanthine oxidase (XO) system was examined as a potential source of superoxide in mice with streptozotocin (STZ)-induced experimental diabetes. Plasma XO activity increased 3-fold in diabetic mice (50 ± 33 μU/ml) 2 weeks after the onset of diabetes, as compared with non-diabetic control mice (15 ± 6 μU/ml). In vivo superoxide generation in diabetic mice was evaluated by an in vivo electron spin resonance (ESR)/spin probe method. Superoxide generation was significantly enhanced in diabetic mice, and the enhancement was restored by the administration of superoxide dismutase (SOD) and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron), which was reported to scavenge superoxide. Pretreatment of diabetic mice with XO inhibitors, allopurinol and its active metabolite oxipurinol, normalized the increased superoxide generation. In addition, there was a correlation (r = 0.78) between the level of plasma XO activity and the relative degree of superoxide generation in diabetic and non-diabetic mice. Hence, the results of this study strongly suggest that superoxide should be generated through the increased XO seen in the diabetic model mice, which may be involved in the pathogenesis of diabetic vascular complications.",
    author = "Shingo Matsumoto and Ichiro Koshiishi and Toyoshi Inoguchi and Hajime Nawata and Hideo Utsumi",
    year = "2003",
    month = "7",
    day = "1",
    doi = "10.1080/1071576031000107344",
    language = "English",
    volume = "37",
    pages = "767--772",
    journal = "Free Radical Research",
    issn = "1071-5762",
    publisher = "Informa Healthcare",
    number = "7",

    }

    TY - JOUR

    T1 - Confirmation of superoxide generation via xanthine oxidase in streptozotocin-induced diabetic mice

    AU - Matsumoto, Shingo

    AU - Koshiishi, Ichiro

    AU - Inoguchi, Toyoshi

    AU - Nawata, Hajime

    AU - Utsumi, Hideo

    PY - 2003/7/1

    Y1 - 2003/7/1

    N2 - Reactive oxygen species (ROS) may play key roles in vascular inflammation and atherogenesis in patients with diabetes. In this study, xanthine oxidase (XO) system was examined as a potential source of superoxide in mice with streptozotocin (STZ)-induced experimental diabetes. Plasma XO activity increased 3-fold in diabetic mice (50 ± 33 μU/ml) 2 weeks after the onset of diabetes, as compared with non-diabetic control mice (15 ± 6 μU/ml). In vivo superoxide generation in diabetic mice was evaluated by an in vivo electron spin resonance (ESR)/spin probe method. Superoxide generation was significantly enhanced in diabetic mice, and the enhancement was restored by the administration of superoxide dismutase (SOD) and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron), which was reported to scavenge superoxide. Pretreatment of diabetic mice with XO inhibitors, allopurinol and its active metabolite oxipurinol, normalized the increased superoxide generation. In addition, there was a correlation (r = 0.78) between the level of plasma XO activity and the relative degree of superoxide generation in diabetic and non-diabetic mice. Hence, the results of this study strongly suggest that superoxide should be generated through the increased XO seen in the diabetic model mice, which may be involved in the pathogenesis of diabetic vascular complications.

    AB - Reactive oxygen species (ROS) may play key roles in vascular inflammation and atherogenesis in patients with diabetes. In this study, xanthine oxidase (XO) system was examined as a potential source of superoxide in mice with streptozotocin (STZ)-induced experimental diabetes. Plasma XO activity increased 3-fold in diabetic mice (50 ± 33 μU/ml) 2 weeks after the onset of diabetes, as compared with non-diabetic control mice (15 ± 6 μU/ml). In vivo superoxide generation in diabetic mice was evaluated by an in vivo electron spin resonance (ESR)/spin probe method. Superoxide generation was significantly enhanced in diabetic mice, and the enhancement was restored by the administration of superoxide dismutase (SOD) and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron), which was reported to scavenge superoxide. Pretreatment of diabetic mice with XO inhibitors, allopurinol and its active metabolite oxipurinol, normalized the increased superoxide generation. In addition, there was a correlation (r = 0.78) between the level of plasma XO activity and the relative degree of superoxide generation in diabetic and non-diabetic mice. Hence, the results of this study strongly suggest that superoxide should be generated through the increased XO seen in the diabetic model mice, which may be involved in the pathogenesis of diabetic vascular complications.

    UR - http://www.scopus.com/inward/record.url?scp=0038476475&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0038476475&partnerID=8YFLogxK

    U2 - 10.1080/1071576031000107344

    DO - 10.1080/1071576031000107344

    M3 - Article

    VL - 37

    SP - 767

    EP - 772

    JO - Free Radical Research

    JF - Free Radical Research

    SN - 1071-5762

    IS - 7

    ER -