Antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicity
The use of chemical warfare agents is an ongoing, significant threat to both civilians and military personnel worldwide. Nerve agents are by far the most formidable toxicants in terms of their lethality and toxicity. Nerve agents initiate neurotoxicity by the irreversible inhibition of acetylcholine...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996119301020 |
| _version_ | 1818728767210651648 |
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| author | Jennifer N. Pearson-Smith Manisha Patel |
| author_facet | Jennifer N. Pearson-Smith Manisha Patel |
| author_sort | Jennifer N. Pearson-Smith |
| collection | DOAJ |
| description | The use of chemical warfare agents is an ongoing, significant threat to both civilians and military personnel worldwide. Nerve agents are by far the most formidable toxicants in terms of their lethality and toxicity. Nerve agents initiate neurotoxicity by the irreversible inhibition of acetylcholinesterase and resultant accumulation of acetylcholine in excitable tissues. The cholinergic toxidrome presents as miosis, lacrimation, diarrhea, fasciculations, seizures, respiratory arrest and coma. Current medical countermeasures can attenuate acute mortality and confer limited protection against secondary neuronal injury when given rapidly after exposure. However, there is an urgent need for the development of novel, add-on neuroprotective therapies to prevent mortality and long-term toxicity of nerve agents. Increasing evidence suggests that pathways other than direct acetylcholinesterase inhibition contribute to neurotoxicity and secondary neuronal injury. Among these, oxidative stress is emerging as a key therapeutic target for nerve agent toxicity. In this review, we discuss the rationale for targeting oxidative stress in nerve agent toxicity and highlight research investigating antioxidant therapy as a neuroprotective medical countermeasure to attenuate oxidative stress, neuroinflammation and neurodegeneration. |
| first_indexed | 2024-12-17T22:35:13Z |
| format | Article |
| id | doaj.art-403e162c3dc446f4ab8432af65ee368e |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T22:35:13Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-403e162c3dc446f4ab8432af65ee368e2022-12-21T21:30:07ZengElsevierNeurobiology of Disease1095-953X2020-01-01133Antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicityJennifer N. Pearson-Smith0Manisha Patel1Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, 80045, United States of AmericaCorresponding author at : 12850 E. Montview Blvd V20-C238, Aurora, CO 80045, United States of America; Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, 80045, United States of AmericaThe use of chemical warfare agents is an ongoing, significant threat to both civilians and military personnel worldwide. Nerve agents are by far the most formidable toxicants in terms of their lethality and toxicity. Nerve agents initiate neurotoxicity by the irreversible inhibition of acetylcholinesterase and resultant accumulation of acetylcholine in excitable tissues. The cholinergic toxidrome presents as miosis, lacrimation, diarrhea, fasciculations, seizures, respiratory arrest and coma. Current medical countermeasures can attenuate acute mortality and confer limited protection against secondary neuronal injury when given rapidly after exposure. However, there is an urgent need for the development of novel, add-on neuroprotective therapies to prevent mortality and long-term toxicity of nerve agents. Increasing evidence suggests that pathways other than direct acetylcholinesterase inhibition contribute to neurotoxicity and secondary neuronal injury. Among these, oxidative stress is emerging as a key therapeutic target for nerve agent toxicity. In this review, we discuss the rationale for targeting oxidative stress in nerve agent toxicity and highlight research investigating antioxidant therapy as a neuroprotective medical countermeasure to attenuate oxidative stress, neuroinflammation and neurodegeneration.http://www.sciencedirect.com/science/article/pii/S0969996119301020Oxidative stressOrganophosphatesAcetylcholinesteraseReactive oxygen species |
| spellingShingle | Jennifer N. Pearson-Smith Manisha Patel Antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicity Neurobiology of Disease Oxidative stress Organophosphates Acetylcholinesterase Reactive oxygen species |
| title | Antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicity |
| title_full | Antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicity |
| title_fullStr | Antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicity |
| title_full_unstemmed | Antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicity |
| title_short | Antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicity |
| title_sort | antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicity |
| topic | Oxidative stress Organophosphates Acetylcholinesterase Reactive oxygen species |
| url | http://www.sciencedirect.com/science/article/pii/S0969996119301020 |
| work_keys_str_mv | AT jennifernpearsonsmith antioxidantdrugtherapyasaneuroprotectivecountermeasureofnerveagenttoxicity AT manishapatel antioxidantdrugtherapyasaneuroprotectivecountermeasureofnerveagenttoxicity |