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 cholinesterázy 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

Differences between acetylcholinesterase (AChE) inhibition in the brain structures following VX and RVX exposure are not known as well as information on the possible correlation of biochemical and histochemical methods detecting AChE activity. Therefore, inhibition of AChE in different brain parts detected by histochemical and biochemical techniques was compared in rats intoxicated with VX and RVX. AChE activities in defined brain regions 30 min after treating rats with VX and Russian VX intramuscularly (1.0 x LD(50)) were determined by using biochemical and histochemical methods. AChE inhibition was less expressed for RVX, in comparison with VX. Frontal cortex and pontomedullar areas containing ncl. reticularis has been found as the most sensitive areas for the action of VX. For RVX, these structures were determined to be frontal cortex, dorsal septum, and hippocampus, respectively. Histochemical and biochemical results were in good correlation (R(xy) = 0.8337). Determination of AChE activity in defined brain structures was a more sensitive parameter for VX or RVX exposure than the determination of AChE activity in the whole-brain homogenate. This activity represents a "mean" of the activities in different structures. Thus, AChE activity is the main parameter investigated in studies searching for target sites following nerve-agent poisoning contributing to better understanding of toxicodynamics of nerve agents.

• MeSH
• acetylcholinesterasa metabolismus   účinky léků   MeSH
• chemické bojové látky otrava   MeSH
• cholinesterasové inhibitory otrava   MeSH
• injekce intramuskulární MeSH
• krysa rodu rattus MeSH
• LD50 MeSH
• mozek enzymologie   účinky léků   MeSH
• organothiofosforové sloučeniny otrava   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH