Biomarkers of Nerve Agents Exposure

Nerve agents (OPC) could be used in terrorist acts. Investigation of longer-lived biomarkers for verification of exposure to toxic compounds is important for diagnosis and prognosis of there intoxications. We study the effects of doses of toxic agent and the times expire after intoxications on the potential biomarkers. In our studies soman and tabun applied at different single doses -1.0 LD50, 0.5 LD50 and 0.1 LD50 were able to cause significant changes of BuChE and AChE in erythrocytes, brain and liver for a period of 10 days after the challenge. Intoxications with different doses of soman and tabun proved that brain and erythrocyte AChE are most sensitive regardless of the dose used. In the same conditions we implement a procedure for analysis of phosphylated BuChE in plasma or serum samples, which is based on reactivation of the phosphylated enzyme with fluoride ions (developed from [2]). The method of fluoride reactivation with further treatment and analysis by gas chromatography represented positive results for soman and tabun poisoning up to the fifth day after exposure, despite the implemented dose. We implement the method of fluoride reactivation in clinical practice. Two incidents with acute poisoning with chlorpyrifos and mixture of chlorpyrifos and diazinon have been investigated. Our studies showed that the method for fluoride reactivation is applicable in clinical practice to cases of intoxications with organophosphorus pesticides with capability to detect reactivated fluorophosphates longer than the original intoxicant and its metabolites could be detected in biological samples. The combination of routine biochemical and analytical methods with fluoride reactivation will improve the diagnosis and prognosis of intoxication with nerve (OPC) agents in case of terrorist acts with these compounds.