High Dose of Pralidoxime Reverses Paraoxon-Induced Respiratory Toxicity in Mice [Turk J Anaesthesiol Reanim]
Turk J Anaesthesiol Reanim. 2018; 46(2): 131-138 | DOI: 10.5152/TJAR.2018.29660  

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

Houzé Pascal1, Berthin Thomas1, Raphalen Jean-herlé2, Hutin Alice2, Baud J Frédéric3
1Laboratoire de Biochimie, Hôpital Universitaire Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France
2Département d’Anesthésie – Réanimation- SAMU de Paris, Hôpital Universitaire Necker-Enfants malades, Assistance Publique-Hôpitaux de Paris (AP-HP), 75015 Paris, France
3UMR-8257. Cognitive Action Group. 45, rue des Saint-Pères. 75006. Paris. Université Paris Descartes, 75006 Paris, France

Objective: The 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 administering an equipotent dose of diethylparaoxon to rats, a 150 mg kg−1 dose of pralidoxime administered alone completely reversed diethylparaoxon-induced respiratory toxicity in mice. The dose dependency of reversal suggests that further studies are needed for assessing plasma concentrations of pralidoxime resulting in reversal of toxicity.

Keywords: Diethylparaoxon, pralidoxime, mice, plethymosgraphy, organophosphates, antidotes.


Houzé Pascal, Berthin Thomas, Raphalen Jean-herlé, Hutin Alice, Baud J Frédéric. High Dose of Pralidoxime Reverses Paraoxon-Induced Respiratory Toxicity in Mice. Turk J Anaesthesiol Reanim. 2018; 46(2): 131-138

Corresponding Author: Houzé Pascal, France


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