Tabun belongs to the most toxic nerve agents. Its mechanism of action is based on acetylcholinesterase (AChE) inhibition at the peripheral and central nervous systems. Therapeutic countermeasures comprise administration of atropine with cholinesterase reactivators able to reactivate the inhibited enzyme. Reactivation of AChE is determined mostly biochemically without specification of different brain structures. Histochemical determination allows a fine search for different structures but is performed mostly without quantitative evaluation. In rats intoxicated with tabun and treated with a combination of atropine and HI-6, obidoxime, or new oxime K048, AChE activities in different brain structures were determined using biochemical and quantitative histochemical methods. Inhibition of AChE following untreated tabun intoxication was different in the various brain structures, having the highest degree in the frontal cortex and reticular formation and lowest in the basal ganglia and substantia nigra. Treatment resulted in an increase of AChE activity detected by both methods. The highest increase was observed in the frontal cortex. This reactivation was increased in the order HI-6 < K048 < obidoxime; however, this order was not uniform for all brain parts studied. A correlation between AChE activity detected by histochemical and biochemical methods was demonstrated. The results suggest that for the mechanism of action of the nerve agent tabun, reactivation in various parts of the brain is not of the same physiological importance. AChE activity in the pontomedullar area and frontal cortex seems to be the most important for the therapeutic effect of the reactivators. HI-6 was not a good reactivator for the treatment of tabun intoxication.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- atropin MeSH
- čelní lalok účinky léků enzymologie patologie MeSH
- chemické bojové látky toxicita MeSH
- cholinesterasové inhibitory aplikace a dávkování toxicita MeSH
- GPI-vázané proteiny metabolismus MeSH
- krysa rodu rattus MeSH
- LD50 MeSH
- mozek účinky léků enzymologie patologie MeSH
- obidoxim chlorid aplikace a dávkování farmakologie terapeutické užití MeSH
- organofosfáty aplikace a dávkování antagonisté a inhibitory toxicita MeSH
- orgánová specificita MeSH
- oximy aplikace a dávkování farmakologie terapeutické užití MeSH
- potkani Wistar MeSH
- pyridinové sloučeniny aplikace a dávkování farmakologie terapeutické užití MeSH
- reaktivátory cholinesterasy aplikace a dávkování farmakologie terapeutické užití MeSH
- retikulární formace účinky léků enzymologie patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
