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Chronic In Vivo Sodium Azide Infusion Induces Selective and Stable Inhibition of Cytochrome c Oxidase
Authors:M Catherine Bennett  Gary W Mlady  Young-Hwa Kwon  †‡ Gregory M Rose
Institution:National Institute on Aging, Laboratory of Neurosciences, National Institutes of Health, Bethesda, Maryland;and; Department of Pharmacology and; Neuroscience Training Program, University of Colorado Health Sciences Center, and; Medical Research Service, Veterans Affairs Medical Center, Denver, Colorado, U.S.A.
Abstract:Abstract: The effect of chronic subcutaneous infusion of sodium azide on the activity of mitochondrial respiratory chain enzymes was investigated in Sprague-Dawley rats. Treatment with ~1 mg/kg/h sodium azide induced chronic, partial inhibition of cytochrome c oxidase, whereas the activities of respiratory complexes I and III were not significantly affected. The inhibition of cytochrome c oxidase was evident by 7 days after infusion began, and the effect was stable for at least 3 weeks. The selectivity of azide for cytochrome c oxidase is discussed in the context of other findings of azide effects on enzymes. The results of the present study indicate that the sodium azide infusion paradigm described here provides a useful tool for the evaluation of selective and stable cytochrome oxidase inhibition in vivo.
Keywords:Complex IV  Electron transport chain  Mitochondria  Oxidative metabolism  Rats
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