title: The role of oxidative stress in organophosphate and nerve agent toxicity.
abstract: Organophosphate (OP) nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent OP toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to OP agents. Key findings of these studies include alterations in mitochondrial function and increased free radical-mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in OP neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of OP-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures.
authors.affiliation: Neuroscience Program.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Pearson
authors.affiliation: Neuroscience Program. Manisha.Patel@ucdenver.edu.|Department of Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, Colorado. Manisha.Patel@ucdenver.edu.
authors.forename: Manisha
authors.initials: M
authors.lastname: Patel
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D006801:Humans; D000067397:Nerve Agents / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000378:metabolism*; D062025:Organophosphate Poisoning / Q000175:diagnosis / Q000378:metabolism*; D010755:Organophosphates / Q000633:toxicity*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002800:Cholinesterase Inhibitors; D000067397:Nerve Agents; D010755:Organophosphates; D017382:Reactive Oxygen Species; D000110:Acetylcholinesterase
keywords: acetylcholinesterase; nerve agents; organophosphates; oxidative stress; reactive oxygen species