Acute and long‐term consequences of exposure to organophosphate nerve agents in humans

Abstract

Summary Nerve agents are organophosphate (OP) compounds and among the most powerful poisons known to man. A terrorist attack on civilian or military populations causing mass casualties is a real threat. The OP nerve agents include soman, sarin, cyclosarin, tabun and VX. The major mechanism of acute toxicity is the irreversible inhibition of acetylcholinesterase (AChE). AChE inhibition results in the accumulation of excessive acetylcholine levels in synapses leading to progression of toxic signs including hypersecretions, tremors, status epilepticus, respiratory distress and death. Miosis and rhinorrhea are the most common clinical findings in those individuals acutely exposed to OP nerve agents. Prolonged seizures are responsible for the neuropathology. The brain region that shows the most severe damage is the amygdala followed by the piriform cortex, hippocampus, cortex, thalamus, and caudate/putamen. Current medical countermeasures are only modestly effective in attenuating the seizures and neuropathology. Anticonvulsants such as benzodiazepines decrease seizure activity and improve outcome but their efficacy depends upon the administration time post-exposure to the nerve agent. Administration of benzodiazepines may increase the risk for seizure recurrence. Recent studies document long-term neurologic and behavior deficits while technological advances demonstrate structural brain changes on magnetic resonance imaging.

Chlorpyrifos- and Dichlorvos-Induced Oxidative and Neurogenic Damage Elicits Neuro-Cognitive Deficits and Increases Anxiety-Like Behavior in Wild-Type Rats

“…Epidemiological studies in humans have linked OP exposure to an increased risk of developing Alzheimer’s disease [25]. Other studies have been carried out to try and establish a link between OP exposure and the incidence of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and have established a collection of symptoms collectively known as COPIND [13,14,15]. Some of these results however could not establish a cause–effect relationship and are therefore inconclusive and still subject to debate and further research [25,26,52].…”

“…In addition, OPs have been implicated in the induction of deleterious oxidative changes in various organs in the body. Their activities with respect to antioxidant free-radical balance are of vital importance, since free radicals are important mediators in the pathophysiology of most neurodegenerative diseases [13]. The neurologic effects of OP toxicity is manifested as chronic organophosphate-induced neuropsychiatric disorder (COPIND), which is characterized by cognitive deficits, depression, anxiety, and some personality problems [14,15].…”

Maintaining Preparedness to Severe Though Infrequent Threats—Can It Be Done?

“…Collective exposure to toxic materials may lead to a chaotic situation, derived from a lack of communication between varied stakeholders and response teams, scarcity of human and material resources, or deficient infrastructure for provision of patient care [3,19,20]. The severe potential consequences of exposure to toxic materials necessitate the establishment of strategies for life-saving procedures, the implementation of an immediate response, a rapid decontamination process, triage of patients, and on-site and hospital medical treatment procedures [21][22][23]. Protocols and Standard Operating Procedures (SOPs) concerning the treatment of contaminated patients need to be established, the systemic operation of medical entities has to be designed and incorporated in the overall healthcare systems' disaster plans, and safety procedures have to be defined and integrated in advance to prevent staff's exposure to toxic materials without adequate protection [7,20].…”

The Role of Molecular Modeling & Simulation in the Discovery and Deployment of Metal-Organic Frameworks for Gas Storage and Separation

“…185,186 Acute exposure to nerve agents can lead to long-term cognitive and behavioral deficits. 187 The adsorption ca-pabilities of MOFs can potentially be exploited to capture chemical warfare agents from the air, 188 e.g., as a filter in a gas mask. 189 Using molecular simulations to rank MOFs according to their ability to capture CWAs underlines a classic role of computer simulations: reducing the need to conduct dangerous experiments.…”