Evidence for contribution of vascular NAD(P)H oxidase to increased oxidative stress in animal models of diabetes and obesity

Toshiyo Sonta, Toyoshi Inoguchi, Hirotaka Tsubouchi, Naotaka Sekiguchi, Kunihisa Kobayashi, Shingo Matsumoto, Hideo Utsumi, Hajime Nawata

    Research output: Contribution to journalArticlepeer-review

    154 Citations (Scopus)

    Abstract

    It is well established that oxidative stress is enhanced in diabetes. However, the major in vivo source of oxidative stress is not clear. Here we show that vascular NAD(P)H oxidase may be a major source of oxidative stress in diabetic and obese models. In vivo electron spin resonance (ESR)/spin probe was used to evaluate systemic oxidative stress in vivo. The signal decay rate of the spin probe (spin clearance rate; SpCR) significantly increased in streptozotocin-induced diabetic rats 2 weeks after the onset of diabetes. This increase was completely normalized by treatment with the antioxidants α-tocopherol (40 mg/kg) and superoxide dismutase (5000 units/kg), and was significantly inhibited by treatment with a PKC-specific inhibitor, CGP41251 (50 mg/kg), and a NAD(P)H oxidase inhibitor, apocynin (5 mg/kg). Both obese ob/ob mice (10 weeks old) with mild hyperglycemia and Zucker fatty rats (11 weeks old) with normoglycemia exhibited significantly increased SpCR as compared with controls. Again, this increase was inhibited by treatment with both CGP41251 and apocynin. Oral administration of insulin sensitizer, pioglitazone (10 mg/kg), for 7 days also completely normalized SpCR values. These results suggest that vascular NAD(P)H oxidase may be a major source of increased oxidative stress in diabetes and obesity.

    Original languageEnglish
    Pages (from-to)115-123
    Number of pages9
    JournalFree Radical Biology and Medicine
    Volume37
    Issue number1
    DOIs
    Publication statusPublished - Jul 1 2004

    All Science Journal Classification (ASJC) codes

    • Biochemistry
    • Physiology (medical)

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