Antioxidant drug therapy as a neuroprotective countermeasure of nerve agent toxicity.
Acetylcholinesterase
Organophosphates
Oxidative stress
Reactive oxygen species
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
07
01
2019
revised:
18
04
2019
accepted:
23
04
2019
pubmed:
28
4
2019
medline:
15
12
2020
entrez:
28
4
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31028872
pii: S0969-9961(19)30102-0
doi: 10.1016/j.nbd.2019.04.013
pmc: PMC7721294
mid: NIHMS1650456
pii:
doi:
Substances chimiques
Antioxidants
0
Nerve Agents
0
Neuroprotective Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
104457Subventions
Organisme : NINDS NIH HHS
ID : R01 NS039587
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS072099
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS039587
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS083422
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
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