Effects of HI-6 on brain neuronal RNA and acetylcholinesterase: metabolic responses during acute soman intoxication.
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 acetyl-cholinesterase (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 micrograms/kg) soman, whereas combined HI-6 + AS treatment only partially restored (cortical) or did not change (striatal) neuron RNA contents. HI-6 produced appreciable 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.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000931:Antidotes; D001285:Atropine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002802:Cholinesterases / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010091:Oximes; D011726:Pyridinium Compounds / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000633:toxicity*
D000931:Antidotes; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D012313:RNA; D001285:Atropine; D012999:Soman; D000110:Acetylcholinesterase; D002802:Cholinesterases; C022870:asoxime chloride