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    The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity

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    Author
    Bordt, Evan A.
    Zhang, Naibo
    Waddell, Jaylyn
    Polster, Brian M.
    Date
    2022-03-01
    Journal
    Antioxidants (Basel, Switzerland)
    Publisher
    MDPI AG
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3390/antiox11030450
    Abstract
    Mitochondrial division inhibitor-1 (mdivi-1), a non-specific inhibitor of Drp1-dependent mi-tochondrial fission, is neuroprotective in numerous preclinical disease models. These include rodent models of Alzheimer’s disease and ischemic or traumatic brain injury. Among its Drp1-independent actions, the compound was found to suppress mitochondrial Complex I-dependent respiration but with less resultant mitochondrial reactive oxygen species (ROS) emission compared with the classical Complex I inhibitor rotenone. We employed two different methods of quantifying Trolox-equivalent antioxidant capacity (TEAC) to test the prediction that mdivi-1 can directly scavenge free radicals. Mdivi-1 exhibited moderate antioxidant activity in the 2,2′-azinobis (3-ethylbenzothiazoline 6-sulfonate) (ABTS) assay. Half-maximal ABTS radical depletion was observed at ~25 µM mdivi-1, equivalent to that achieved by ~12.5 µM Trolox. Mdivi-1 also showed antioxidant activity in the α, α-diphenyl-β-picrylhydrazyl (DPPH) assay. However, mdivi-1 exhibited a reduced capacity to deplete the DPPH radical, which has a more sterically hindered radical site compared with ABTS, with 25 µM mdivi-1 displaying only 0.8 µM Trolox equivalency. Both assays indicate that mdivi-1 possesses biochemical antioxidant activity but with modest potency relative to the vitamin E analog Trolox. Future studies are needed to evaluate whether the ability of mdivi-1 to directly scavenge free radicals contributes to its mechanisms of neuroprotection. © 2022 by the authors.
    Sponsors
    National Institutes of Health
    Keyword
    Complex I
    Free radical
    Mitochondria
    Mitochondrial fission
    Neurons
    Oxidative stress
    Oxygen
    ROS
    Scavenger
    Superoxide
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/18151
    ae974a485f413a2113503eed53cd6c53
    10.3390/antiox11030450
    Scopus Count
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