The NADPH Oxidase Inhibitor, Mitoapocynin, Mitigates DFP-Induced Reactive Astrogliosis in a Rat Model of Organophosphate Neurotoxicity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.1.1. Nanoparticle Synthesis and Characterization
2.1.2. MPO Loading and Release Kinetics
2.2. Animals
2.3. DFP Challenge, SE Monitoring, and Dosing Regimens
2.4. Euthanasia and Tissue Collection
2.5. Mitoapocynin Extraction and Quantification
2.5.1. Extraction of Mitoapocynin from Sera and Brain Tissue for LC-MS/MS
2.5.2. Mitoapocynin LC-MS/MS Quantification
2.6. Immunohistochemistry and Fluoro-Jade B Staining (FJB)
2.7. Imaging, Cell Quantification, and Morphometric Analysis
2.8. Statistical Analyses
3. Results
3.1. MPO-NP and MPO-Oral Concentrations in the Brain and Serum Post-DFP
3.2. MPO-Oral Modifies Neuronal Loss Post-DFP
3.3. MPO-Oral Mitigates GABAergic Neuronal Loss in the CA1 Hippocampal Region Post-DFP
3.4. MPO-Oral and MPO-NP Treatment Did Not Affect NOX2 (GP91phox) Expression Post-DFP
3.5. DFP-Exposure Promoted Microglial Reactivity
3.6. MPO-Oral and MPO-NP Attenuated Astrogliosis and Their Reactivity 8 Days Post-DFP
3.7. Kir4.1 Is Downregulated in Astrocytes after DFP Exposure
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Meyer, C.; Grego, E.; S. Vasanthi, S.; Rao, N.S.; Massey, N.; Holtkamp, C.; Huss, J.; Showman, L.; Narasimhan, B.; Thippeswamy, T. The NADPH Oxidase Inhibitor, Mitoapocynin, Mitigates DFP-Induced Reactive Astrogliosis in a Rat Model of Organophosphate Neurotoxicity. Antioxidants 2023, 12, 2061. https://doi.org/10.3390/antiox12122061
Meyer C, Grego E, S. Vasanthi S, Rao NS, Massey N, Holtkamp C, Huss J, Showman L, Narasimhan B, Thippeswamy T. The NADPH Oxidase Inhibitor, Mitoapocynin, Mitigates DFP-Induced Reactive Astrogliosis in a Rat Model of Organophosphate Neurotoxicity. Antioxidants. 2023; 12(12):2061. https://doi.org/10.3390/antiox12122061
Chicago/Turabian StyleMeyer, Christina, Elizabeth Grego, Suraj S. Vasanthi, Nikhil S. Rao, Nyzil Massey, Claire Holtkamp, Joselyn Huss, Lucas Showman, Balaji Narasimhan, and Thimmasettappa Thippeswamy. 2023. "The NADPH Oxidase Inhibitor, Mitoapocynin, Mitigates DFP-Induced Reactive Astrogliosis in a Rat Model of Organophosphate Neurotoxicity" Antioxidants 12, no. 12: 2061. https://doi.org/10.3390/antiox12122061