Abstract
Acetylcholinesterase (AChE) activities in different brain parts were determinedquantitatively in rats treated with huperzine A, soman, and huperzine A followed bysoman, using histochemical and biochemical methods. Following soman intoxication (1.2x LD50, i.m.), AChE activity was decreased to 30-80% of control values depending on thebrain structure. The most sensitive area was the frontal cortex and the most relativelyresistant was ncl. ruber. Huperzine A treatment only caused a change in AChE activityvarying from 70 to 100 % of control values. In rats pretreated with huperzine A andintoxicated with soman, AChE activity was significantly higher than that observed aftersoman. In these animals, survival of rats pretreated with huperzine was observed whilethe mortality of unpretreated animals was near to 80 %. The results suggest that huperzineA is good candidate for further study for clinical use as a prophylactic drug against nerveagent poisoning.
Highlights
Nerve agents belong to the most toxic organophosphorus cholinesterase inhibitors
After administration of huperzine A, fine tremor was observed occuring 1030 min post administration, as well as in a group of animals pretreated with huperzine A and intoxicated with soman
At the light of its particular inhibitory affects on the brain AChE activity, huperzine, compared to the other drugs, seems to be the optimal candidate to be used as pretreatment against OP poisoning [8,9] as demonstrated in guinea-pigs
Summary
Nerve agents belong to the most toxic organophosphorus cholinesterase inhibitors. They can be used as chemical warfare agents and, they can be (and have been) misused by terrorists. The review of Jiang et al [7] represents a comprehensive documentation of the progress in the studies on huperzine A covering the period 1999-2002 It appears to be a selective inhibitor of red cell AchE, while pyridostigmine or physostigmine inhibit plasmatic butyrylcholinesterase (BuChE, EC 3.1.1.8) in guinea-pigs [8,9]. It is difficult to correlate biochemical results which are not defined structurally as those in histochemical studies This approach (comparison of these results) was used [20] and showed that it is possible and it would be interesting approach allowing more detailed explanation of action of nerve agents as well as their therapeutic influencing. (on the basis of above mentioned studies), prophylactic effects of huperzine A against soman using determination of AChE activity (histochemical and biochemical) in selected rat brain structures was studied
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