Quantitative cytochemical techniques were used to monitor effects of the bis-pyridinium oxime HI-6 with and without atropine sulfate (AS) on soman-induced cerebrocortical (layer V) and striatal neuron RNA and acetylcholinesterase (AChE) impairments. In addition, plasma cholinesterase (ChE) activity was measured to determine the extent of peripheral enzyme reactivation. Antidotal pretreatment effected complete (HI-6) or partial (AS) amelioration of neuronal RNA depletion evidenced following 1.5 LD50 (195 μg/kg) soman, whereas combined HI-6 + AS treatment only partially restored (cortical) or did not change (striatal) neuron RNA contents. HI-6 produced appreaciable plasma ChE reactivation but brain AChE activity was not significantly altered. In rats treated only with antidotes, HI-6 or AS alone significantly reduced neuronal RNA in both brain regions. These data indicate that HI-6 influences the metabolic status of central cholinergic compartments and can completely protect against soman-induced neuronal RNA depletion. However, there are no precise relationships among RNA restitution, AChE reactivation or the protective potency of antidotal treatments. Effects of HI-6 on neuronal RNA may signify central cholinolytic activity in vivo, but indirect effects mediated by peripheral mechanisms can not be excluded at present.
- Acute soman toxication
- Central metabolic impairments
- Neuronal RNA depletion
- Quantitative RNA cytophotometry
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