The effect of various organophosphorus (OP) compounds on 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNP) activity and the relationship to neurotoxic response was studied. Adult White Leghorn hens were dosed with either diisopropyl fluorophosphate (DFP), tri-o-cresyl phosphate (TOCP), leptophos, or paraoxon. CNP activity was determined utilizing crude homogenates or purified myelin preparations from whole brain, spinal cord, and sciatic nerves at maximal neurologic dysfunction, evaluated as locomotor impairment. Enzyme assays of CNP revealed a decrease in brain CNP activity at the time of maximal locomotor impairment after a single, oral dose of leptophos. Decreased CNP activity was also noted in spinal cord preparations from DFP-treated hens at the time of maximal locomotor impairment. Sciatic nerve CNP activity was not altered following treatment with OP-compounds. Paraoxon, a non-neurotoxic OP-compound, had little effect on neural tissue CNP activity. Neurotoxic OP-compounds, that cause secondary degeneration of myelin (Wallerian), may be associated with decreased brain and spinal cord CNP activity at the time of maximal locomotor impairment.
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