engleski

Reduction of paraoxon toxicity by oxime K048: In vivo study focused on ChE/AChE activity

Organophosphorous (OP) pesticides are in wide use around the world and a significant number of poisonings and deaths are reported each year as a result of exposure to them. OP insecticide parathion, whose active metabolite is paraoxon, has a major contribution to occupational and accidental intoxications. The acute toxicity of OP pesticides is primarily attributed to irreversible inhibition of acetylcholinesterase (AChE), an enzyme vital to normal nerve function. The inability of the conventional therapy to provide adequate protection against these intoxications calls for a synthesis of new compounds with the characteristic oxime group. In the present study, we investigated efficacy of oxime K048 by using a rat model. ChE/AChE activity was measured in rat plasma, brain and diaphragm 0.5, 1, 6 and 24 h upon paraoxon poisoning and applied oxime plus atropine therapy. Degree of inhibition and temporal distribution of the cholinesterase activity after exposure to paraoxon were similar in all observed organs but it is important to stress that enzyme activity in both plasma and tissues did not return to normal even after 24 h (max. 37%). A combination of K048 and atropine afforded high potency in restoring the activity of ChE in plasma by achieving 50-60% of reactivation efficacy up to 6 h and by completely reactivating plasma ChE after 24 h. The applied therapy also increased AChE activity in tissues although the reactivation potency did not surpassed 20%. Our results reveal marked improvement in counteracting paraoxon poisoning probably due to good reactivation potential of oxime K048.

paraoxon ; oxime ; rat ; plasma ; brain ; diaphragm ; acetylcholinesterase

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