VZL 2004, 73(4):142-144
The Effect of Repeated Antidotal Treatment on Tabun-Induced Toxicity in Mice
- Jiří Kassa
ORCID... - Katedra toxikologie Vojenské lékařské akademie J. E. Purkyně, Hradec Králové
V pokusech na samcích myší kmene NMRI byl testován vliv jednorázově nebo opakovaně podané antidotní terapie různými oximy (pralidoxim, obidoxim, trimedoxim, oxim HI-6) v kombinaci s anticholinergikem atropinem na akutní toxicitu organofosforové sloučeniny tabunu cestou ovlivnění střední smrtné dávky (LD50) při 24hodinovém přežívání tabunem otrávených pokusných zvířat.
Pokud je některý z testovaných oximů v kombinaci atropinem podáván opakovaně v průběhu akutní intoxikace tabunem, dochází k mírnému, nesignifikantnímu vzestupu hodnoty LD50 oproti jednorázovému podání téže antidotní kombinace pouze v případě použití pralidoximu nebo obidoximu jako reaktivátoru acetylcholinesterázy. To znamená, že opakované podání sledovaných kombinací antidot nevede ke statisticky významnému zlepšení efektu léčby u akutní intoxikace tabunem. Srovnání terapeutického efektu sledovaných oximů ukázalo, že trimedoxim se jeví jako nejvhodnější oxim ke snížení akutní toxicity tabunu.
Získané výsledky potvrdily, že ze současných reaktivátorů acetylcholinesterázy se ani jeden nejeví jako dostatečně účinný pro eliminaci akutní toxicity tabunu. Jako perspektivní reaktivátor acetylcholinesterázy se pro terapii akutních otrav tabunem nabízí trimedoxim. Opakované podání antidot v průběhu akutní intoxikace tabunem nevede k pronikavějšímu zlepšení efektu léčby.
Keywords: Tabun; Pralidoxim; Obidoxim; Trimedoxim; HI-6; Atropin; LD50; Myš
Male NMRI mice were used to test the effect of single or repeated antidotal treatment with various oximes (pralidoxime, obidoxime, trimedoxime, the oxime HI-6) in combination with an anticholinergic drug atropine on the acute toxicity of organophosphorus tabun compound with the help of evaluating medial lethal (LD50) dose at a 24-hour survival of tabun-poisoned experimental animals.If some of the tested oximes in combination with atropine were administered repeatedly during acute tabun intoxication, a slight increase in the LD50 value was observed compared to a single administration when pralidoxime or obidoxime was used as an acetylcholinesterase reactivator. This means that the repeated administration of observed antidotal mixtures does not bring a significant improvement in the efficacy of antidotal treatment of acute tabun poisoning. The comparison of the therapeutic effects of tested oximes shows that trimedoxime seems to be the most suitable oxime for decreasing the acute tabun toxicity.The results confirm that no currently used oxime is sufficiently effective for eliminating acute tabun toxicity. Trimedoxime appears to be a prospective acetylcholinesterase reactivator for the antidotal treatment of tabun poisoning. The repeated administration of antidotes during acute tabun poisoning does not show a significant increase in the therapeutical efficacy of antidotal treatment of acute tabun poisoning.
Keywords: Tabun, Pralidoxime; Obidoxime; Trimedoxime; HI-6; Atropine; LD50; Mouse
Received: March 5, 2004; Published: December 1, 2004 Show citation
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