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dc.contributor.authorBordt, Evan A.
dc.contributor.authorZhang, Naibo
dc.contributor.authorWaddell, Jaylyn
dc.contributor.authorPolster, Brian M.
dc.date.accessioned2022-03-04T12:45:40Z
dc.date.available2022-03-04T12:45:40Z
dc.date.issued2022-03-01
dc.identifier.urihttp://hdl.handle.net/10713/18151
dc.description.abstractMitochondrial 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.en_US
dc.description.sponsorshipNational Institutes of Healthen_US
dc.description.urihttps://doi.org/10.3390/antiox11030450en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofAntioxidants (Basel, Switzerland)en_US
dc.subjectComplex Ien_US
dc.subjectFree radicalen_US
dc.subjectMitochondriaen_US
dc.subjectMitochondrial fissionen_US
dc.subjectNeuronsen_US
dc.subjectOxidative stressen_US
dc.subjectOxygenen_US
dc.subjectROSen_US
dc.subjectScavengeren_US
dc.subjectSuperoxideen_US
dc.titleThe Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activityen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/antiox11030450
dc.source.journaltitleAntioxidants
dc.source.volume11
dc.source.issue3


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