Miroslav Pohanka*, Ladislav Novotny, Josef Fusek and Jiri Pikula
The oxime reactivators, obidoxime and asoxime (HI-6) are suitable for antidotal treatment after exposure to nerve agents. Although they are considered for use in humans under emergency situations, complete clinical studies are lacking as there were no clinical trials. We examined obidoxime and HI-6 in laboratory rats intramuscularly exposed to 25% of the median lethal dose (210 and 780 mg/kg) of each oxime reactivator and sacrificed 40 min after exposure. Brain and liver ferric reducing antioxidant power, reduced glutathione (GSH), glutathione reductase, thiobarbituric acid reactive substances, acetylcholinesterase, caspase 3 and glutathione S-transferase were assessed using standard protocols. We found significant depletion of liver and brain low molecular weight antioxidants. On the other hand, the depletion was partially recovered by an increase in the GSH level. Obidoxime was implicated in alteration of apoptotic processes in brain. Overall effects of oxime reactivators are discussed in this study. The pertinent adverse effects and strong modulation of disparate parameters of oxime reactivators, HI-6 and obidoxime are not well understood in antidotal treatment. We found strong impact of oxime reactivators on redox homeostasis and apoptotic processes.
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