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

Mitochondrial division inhibitor-1 (mdivi-1), a non-specific inhibitor of Drp1-dependent mitochondrial 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, th...

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Autores principales: Bordt, Evan A., Zhang, Naibo, Waddell, Jaylyn, Polster, Brian M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944504/
https://www.ncbi.nlm.nih.gov/pubmed/35326100
http://dx.doi.org/10.3390/antiox11030450
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author Bordt, Evan A.
Zhang, Naibo
Waddell, Jaylyn
Polster, Brian M.
author_facet Bordt, Evan A.
Zhang, Naibo
Waddell, Jaylyn
Polster, Brian M.
author_sort Bordt, Evan A.
collection PubMed
description Mitochondrial division inhibitor-1 (mdivi-1), a non-specific inhibitor of Drp1-dependent mitochondrial 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.
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spelling pubmed-89445042022-03-25 The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity Bordt, Evan A. Zhang, Naibo Waddell, Jaylyn Polster, Brian M. Antioxidants (Basel) Communication Mitochondrial division inhibitor-1 (mdivi-1), a non-specific inhibitor of Drp1-dependent mitochondrial 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. MDPI 2022-02-24 /pmc/articles/PMC8944504/ /pubmed/35326100 http://dx.doi.org/10.3390/antiox11030450 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Bordt, Evan A.
Zhang, Naibo
Waddell, Jaylyn
Polster, Brian M.
The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity
title The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity
title_full The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity
title_fullStr The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity
title_full_unstemmed The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity
title_short The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity
title_sort non-specific drp1 inhibitor mdivi-1 has modest biochemical antioxidant activity
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944504/
https://www.ncbi.nlm.nih.gov/pubmed/35326100
http://dx.doi.org/10.3390/antiox11030450
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