Inhibition of cholinesterases following percutaneous intoxication with V agents in rats

Abstract

Female Wistar rats were percutaneously (p.c.) intoxicated (1xLD₅₀) with VX and its two derivatives differing in their substitution on nitrogen (diethyl- and dibutyl- derivatives). Blood cholinesterase activity was continuously monitored; 100 min after the intoxication (or after death), acetylcholinesterase (AChE) activity was determined in diaphragm and brain parts (pontomedullar area – PM, frontal cortex – FC, and basal ganglia – BG). Blood ChE activity remains unchanged at very short interval (5 min) after VX administration; this interval was prolonged for diethyl- and dibutyl derivatives. AChE activity was decreased to 20–30% of control values in diaphragm, then in FC (60–70%) and PM (54–74%). AChE activity in BG was relatively resistant (cca 80%). When the AChE activity was compared for all three agents in relationship to survival (11 animals) or death (7 animals), significant differences between the activities in survived (32%) and died (13%) rats were demonstrated in diaphragm but not in the blood. This tendency (higher AChE activity in survived animals) was also observed in PM and FC, however, not statistically significant. It is concluded that both parts of the molecule – substitution on nitrogen atom and the rest of agent molecule (phosphorus head) probably influence penetration through the skin and simultaneously AChE inhibition. As hypothesis, AChE activity in diaphragm could be important for survival or death in case of acute p.c. intoxication with these types of V agents.

Keywords:

• VX
• derivatives
• blood
• rat
• diaphragm
• brain parts
• acetylcholinesterase
• percutaneous intoxication

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

The study was supported by the grant of Ministry of Defense, a long term organization development plan Medical aspects of weapons of mass destruction. This work was also supported by Long-term development plan UHHK and UHK.