Summary
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 = E 600 and parathion = E 605) 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 μg/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.
Zusammenfassung
Die Reduktion oder vollständige Hemmung der histochemisch nachweisbaren Acetylcholinesterase (AChE)-Aktivität nach experimentellen und spontanen (menschlichen) Organophosphatvergiftungen (besonders mittels Paraoxon = E 600 und Parathion = E 605) muß als Zeichen einer in vivo-Hemmung des cholinergen Systems interpretiert werden. Im Tierversuch wurde eine Beziehung zwischen der AChE-Aktivität und applizierten Dosis der Organophosphate nachgewiesen. In einem in vitro-System konnte die Enzymhemmung nach Exposition von AChE-enthaltenden histologischen Schnitten mit Organophosphat-enthaltenden Körperflüssigkeiten bzw. angesetzten Lösungen festgestellt werden. Bei Untersuchung der Dosisabhängigkeit wurde ferner festgestellt, daß mindestens 0.15 μg/ml Paraoxon oder 5 mg/ml Parathion notwendig sind, um in vitro die AChE zu blockieren. Bei Anwendung desselben in vitro-Systems konnte eine Halbwertzeit für das Paraoxoninaktivierende Enzym im Blut von 6–7 min nachgewiesen werden. Die in vivo und in vitro gehemmte AChE war bei anschließender Behandlung der Schnitte mit Toxogonin reaktivierbar; die Möglichkeit der Reaktivation erlaubt eine qualitative Zuordnung des AChE-hemmenden Toxins zu den Alkylphosphaten. Eine postmortale Persistenz der Enzymhemmung war am menschlichen Material für ca. 2 Monate nachweisbar. Da auch die Acetylcholinesterase in weitgehend unveränderter Aktivität nach einem postmortalen Intervall von wenigstens 70 h nachweisbar ist, muß der histochemische Nachweis als morphologisches Äquivalent einer akuten Organophosphatintoxikation angesehen werden.
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Dedicated to Prof. Dr. J. Peiffer on occasion of his 60th birthday
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Oehmichen, M., Besserer, K. Forensic significance of acetylcholine esterase histochemistry in organophosphate intoxication. Z Rechtsmed 89, 149–165 (1982). https://doi.org/10.1007/BF01873797
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DOI: https://doi.org/10.1007/BF01873797