engleski

Acetylcholinesterase activity in selected regions of the rat brain following paraoxon intoxication and concurrent therapy

Organophosphate pesticides and nerve agents are characterized as compounds influencing cholinergic nerve transmission via inhibition of acetylcholinesterase (AChE). The brain is primary target, since the induced toxic effects on brain are life threatening. Identifying the brain regions that are most vulnerable to organophosphates can facilitate the development of effective antidotes that will reduce damage after exposure. The aim of this study was to determine AChE activity in selected brain regions and whole brain at four different time points (0.5, 1, 6 and 24 h) in paraoxon poisoned rats as well as reactivatability of paraoxon-inhibited AChE after treatment with oxime K048 and atropine. Paraoxon administration markedly inhibited cortical AChE activity (around 50%). The rank order of inhibition in other regions from high to low was septum>pontomedullar area (PM)≥cerebellum>thalamus and hypothalamus (TH). Such inhibition was maintained till 24 h after poisoning which correlates well with the inhibition of enzyme activity in the whole brain. Paraoxon inhibited AChE was generally not affected by the oxime treatment, with three exceptions. In the cortex, PM and TH treatment with K048 and atropine elevated AChE activity during the first hour but the reactivation potency did not exceed 20%. Observed different levels of inhibition underline the fact that protection of AChE have different importance for various brain structures. No marked differentiation of AChE activity between poisoned and treated rats could be due to oxime's limiting penetration through blood-brain barrier.

acetylcholinesterase; brain regions; paraoxon; therapy

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