[Turk J Anaesthesiol Reanim]
Turk J Anaesthesiol Reanim. Baskýdaki Makaleler: TARD-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 poisonings is still a matter of debate. In a rat model, we showed that pralidoxime induced a complete but concentration-dependent reversal of paraoxon-induced respiratory toxicity. The aim of the 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 given subcutaneously to male F1B6D2 mice. Ascending single doses of pralidoxime of 10, 50 to 100, and 150 mg kg-1 were administered intramuscularly 30 min after diethylparaoxon. Ventilation at rest was assessed using whole body plethysmography and mice temperature using infra-red telemetry. Results are expressed as mean +/- SE. Statistical analysis used non-parametric ANOVA tests.
Results: From 30 to 150 minutes 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 increasing in tidal volume. In the 10, 50, and 100 mg.kg-1 pralidoxime groups, there was a trend toward 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: The present study showed a toxic but non-lethal model of diethylparaoxon in awake, unrestrained mice. 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 the interest of further studies assessing the plasma concentrations of pralidoxime resulting in reversal of toxicity.

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

Sorumlu Yazar: Houzé Pascal, France

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