Abstract
The acute toxicity of organophosphates (OPs) in mammals is primarily due to their irreversible inhibition of acetylcholinesterase in the nervous system which leads to increased synaptic acetylcholine levels. However, the toxic effect of some OPs is not limited to inhibition of cholinesterase: following the cholinergic crisis changes in non-cholinergic neurotoxic parameters, such as specific damage to cell membranes, are observed. One of the major problems in assessing the role of lipid peroxydation in any chemical toxicity is to resolve whether this pathogenic cascade is a cause or a consequence of damage. The present study was undertaken to elucidate the relations between lipid peroxidation, OPs toxicity and delayed, long lasting, non-cholinergic changes. We studied the influence of OP intoxication on lipid peroxidation in rat cerebral hemispheres. The level of lipid peroxidation was measured as the amount of common phospholipids, peroxidate lipids and malondialdehyde (MDA) in reaction with thiobarbituric acid. Results were compared to those with pre-treatment with atropine and reversible cholinesterase inhibitor — galanthamine alone or together with different antioxidants. OPs caused a rapid, dose-dependent increase of peroxidate lipids and MDA 15–30 days after intoxication. The level of lipid peroxidation correlated with the rate of conditioned reflex reaction. With paraoxon and sarin pre-treatment with atropine and galan-thamine totally prevents the all symptoms of intoxication and changes in lipid per-oxidation. Comparatively such type of prophylaxis in soman poisoned rats didn't normalize the biochemical and physiological parameters. The protective effect of antioxidants against soman — induced lipid peroxidation was shown. Therefore soman — associated lipid peroxidation is likely to arise mainly as a primary change which may, however, play a significant role in delayed neurotoxicity and conditioned reflex activity.
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