High Dose of Pralidoxime Reverses Paraoxon-Induced Respiratory Toxicity in Mice

Authors
P Houze_, T Berthin , J-H Raphalen , A Hutin , JF Baud


Lab
Cognitive Action Group, Universite_ Paris Descartes, Paris, France

Journal
Turkish Journal of the Anaesthesiology and Reanimation

Abstract
Objective: Thee efficiency of pralidoxime in the treatment of human organophosphates poisoning is still unclear. In a rat model, we showed that pralidoxime induced a complete but concentration-dependent reversal of paraoxon-induced respiratory toxicity. The aim of this study was to assess the efficiency of pralidoxime in a species other than rats.
Methods: A dose of diethylparaoxon corresponding to 50% of the median lethal dose was administered subcutaneously to male F1B6D2 mice. Ascending single pralidoxime doses of 10, 50-100 and 150 mg kg_1 were administered intramuscularly 30 min after diethylparaoxon administration. Ventilation at rest was assessed using whole-body plethysmography and mice temperature was assessed using infrared telemetry. Results are expressed as mean±SE. Statistical analysis used non-parametric tests.
Results: From 30 to 150 min post-injection, diethylparaoxon induced clinical symptoms and a decrease in respiratory frequency, which resulted from an increase in expiratory and inspiratory times associated with an increase in the tidal volume. In the 10-, 50- and 100-mg kg_1 pralidoxime groups, there was a trend towards a non-significant improvement of paraoxon-induced respiratory toxicity. The 150 mg kg_1 dose of pralidoxime induced a significant reversal of all respiratory parameters.
Conclusion: In the present study, a toxic but non-lethal model of diethylparaoxon in awake, unrestrained mice was observed. By ad- ministering an equipotent dose of diethylparaoxon to rats, a 150 mg kg_1 dose of pralidoxime administered alone completely reversed di- ethylparaoxon-induced respiratory toxicity in mice. e dose dependency of reversal suggests that further studies are needed for assessing plasma concentrations of pralidoxime resulting in reversal of toxicity

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