Forensic significance of acetylcholine esterase histochemistry in organophosphate intoxication. Original investigations and review of the literature.
The reduction of acetylcholine esterase (AChE) activity or the complete blocking of AChE to be observed by histochemical demonstration of AChE in tissue after experimental and spontaneous (human) organophosphate intoxication (especially paraoxone = E600 and parathion = E605) should be interpreted as an indication of an in vivo inhibition of the cholinergic system. In animal experiments, a relationship was demonstrated between AChE activity and the applied dose of organophosphorous compounds. In addition, enzyme inhibition was observed in in vitro systems using AChE-containing mouse tissue sections pretreated with organophosphate solutions or with body fluids containing organophosphates. Examination of the concentration dependency indicated that the inhibiting solution must contain at least 0.15 microgram/ml paraoxone or 5 mg/ml parathion to block AChE in the section. Using the same in vitro system, a half-life of 6-7 min was established for the paraoxone inactivating enzyme in blood. The in vivo and in vitro inhibited AChE was reactivated by consecutive treatment of blocked sections with toxogonin. This possibility of reactivation therefore allows qualitative classifications of the AChE-inhibiting toxin to the alkylphosphates. The postmortem persistence of the AChE inhibitory effect was demonstrable for about a 2-month interval. Since the histochemically demonstrable activity of the enzyme AChE is more or less constant during a postmortem interval of at least 70h, the model of histochemical demonstration is a method which provides a morphological equivalent for acute organophosphate intoxication.
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003964:Diaphragm / Q000294:innervation; D004305:Dose-Response Relationship, Drug; D005260:Female; D005554:Forensic Medicine; D007583:Jejunum / Q000294:innervation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009045:Motor Endplate / Q000187:drug effects / Q000201:enzymology; D009132:Muscles / Q000294:innervation; D009469:Neuromuscular Junction / Q000187:drug effects / Q000201:enzymology; D009768:Obidoxime Chloride / Q000506:poisoning*; D010091:Oximes / Q000506:poisoning*; D010261:Paraoxon / Q000506:poisoning*; D010278:Parathion / Q000506:poisoning*
D010091:Oximes; D009768:Obidoxime Chloride; D010278:Parathion; D000110:Acetylcholinesterase; D010261:Paraoxon