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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/3/450 |
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| author | Evan A. Bordt Naibo Zhang Jaylyn Waddell Brian M. Polster |
| author_facet | Evan A. Bordt Naibo Zhang Jaylyn Waddell Brian M. Polster |
| author_sort | Evan A. Bordt |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T13:53:37Z |
| format | Article |
| id | doaj.art-f480accc42d24238a1b13004d5ad3753 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T13:53:37Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-f480accc42d24238a1b13004d5ad37532023-11-30T20:47:27ZengMDPI AGAntioxidants2076-39212022-02-0111345010.3390/antiox11030450The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant ActivityEvan A. Bordt0Naibo Zhang1Jaylyn Waddell2Brian M. Polster3Center for Shock, Trauma and Anesthesiology Research, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Shock, Trauma and Anesthesiology Research, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USADepartment of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USACenter for Shock, Trauma and Anesthesiology Research, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USAMitochondrial 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.https://www.mdpi.com/2076-3921/11/3/450ROSoxidative stressfree radicalscavengersuperoxideoxygen |
| spellingShingle | Evan A. Bordt Naibo Zhang Jaylyn Waddell Brian M. Polster The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity Antioxidants ROS oxidative stress free radical scavenger superoxide oxygen |
| 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 | ROS oxidative stress free radical scavenger superoxide oxygen |
| url | https://www.mdpi.com/2076-3921/11/3/450 |
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