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

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

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    96 Citations (Scopus)


    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
    Issue number7
    Publication statusPublished - Jul 1 2003

    All Science Journal Classification (ASJC) codes

    • Biochemistry


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