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

DEMANDE DE PUBLICATION

Merci de votre intérêt pour notre gamme de produits et de votre demande pour cette publication qui vous sera envoyée si l'équipe de recherche et la revue le permettent. Notre équipe commerciale vous contactera dans les plus brefs délais.