Soman belongs to the most dangerous nerve agents because of the low effectiveness of the presently available antidotes. Soman acts by inhibiting acetylcholinesterase (AChE) both peripherally and centrally, with a subsequent accumulation of neuromediator acetylcholine and other metabolic changes. From the data published in literature it can be concluded that exposure to nerve agents leading to acute effects or chronic exposure to nerve agents may lead to delayed and persistent adverse effects. The aim of this study was to demonstrate changes in AChE and butyrylcholinesterase (BuChE) activities, stressogenic markers (i.e., tyrosine aminotransferase [TAT] activity, and plasma corticosterone level), and neuroexcitability and behavior 24 h and 4 wk following a single soman inhalation exposure at low level. AChE activity in erythrocytes and BuChE activity in plasma was decreased (dependent on the dose of soman) 24 h and 4 wk after the exposure. A similar decrease in AChE activity in different brain parts was observed. One of the stressogenic parameters, TAT, was changed 24 h after exposure only. Behavior of experimental animals was changed 24 h after the exposure, and 4 behavioral parameters persisted 4 wk after the exposure. Neuroexcitability was increased at 24 h after the exposure and had become about normal 4 wk after the exposure. Summarizing, long-term effects (4 wk) were observed after inhalation exposure of guinea pigs to sublethal concentrations of soman.
1. Long term effects of low doses of highly toxic organophosphorus agent sarin on behavioral and neurophysiological functions were studied in rats exposed to sarin by inhalation. The toxic effects of sarin were monitored using a functional observational battery (FOB), an automatic measurement of motor activity and a test of excitability of central nervous system at 3, 6 and 12 months following sarin exposure. 2. The results indicate that sarin at symptomatic as well as asymptomatic doses (level 2 and 3) is able to induce some neurotoxic effects (a decrease in activity and mobility, an alteration of gait, an increase in stereotyped behavior) including an increase in the excitability of central nervous system (an increase in convulsive activity following the administration of pentamethylenetetrazole) in rats at 3 months following inhalation exposure. Some sings of increased excitability were also observed in sarin-exposed rats following 6 or 12 months (an increase in exploratory activity, body temperature and a hindlimb grip strength at 6 months following exposure to sarin at asymptomatic doses, an increase in tail-pinch response at 12 months following exposure to sarin at symptomatic doses). 3. Therefore, nerve agents such as sarin seem to be harmful not only at high, clinically symptomatic doses but also at low, clinically asymptomatic doses because of long term manifestation of alteration of neurophysiological functions in sarin-exposed rats without disruption of cholinergic nervous system.
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