Ventilatory effects of low-dose paraoxon result from central muscarinic effects

Paraoxon induces respiratory toxicity. Atropine completely reversed parathion- and paraoxon-induced respiratory toxicity. The aim of this study was to assess the peripheral or central origin of ventilatory effects of low-dose paraoxon. Male Sprague-Dawley rats were given paraoxon 0.215 mg/kg Subcutaneously and treated with either atropine (10 mg/kg sc) or ascending doses of methylatropine of 5.42 (equimolar to that of atropine), 54.2, and 542 mg/kg administered Subcutaneously 30 Loin after paraoxon. Ventilation at rest was assessed using whole-body plethystriography and rat temperature using infra-red telemetry. Results are expressed as mean SE. Statistical analysis used two-way ANOVA for repeated measurements. Paraoxon induced a significant decrease in temperature 30 min after injection lasting the 90 Loin of the Study period. This effect was partially corrected by atropine, but not by methylatropine whatever the dose. Paraoxon induced a decrease in respiratory rate resulting from all increase in expiratory time associated with an increase in tidal Volume. Atropine completely reversed the ventilatory effects of low-close paraoxon while the equimolar (lose of methylatropine had no significant effects. The 54.2 and 542 doses of methylatropine had no significant effects. Atropine crosses the blood-brain barrier and reverses peripheral and central muscarinic effects. In contrast, methylatropine does not cross the blood-brain barrier. Atropine completely reversed the ventilatory effects of low-close paraoxon, while methylatropine had no significant effects at doses up to 100-fold the equimolar dose of atropine. We conclude that the ventilatory effects of low-dose paraoxon are mediated by disrupted muscarinic signaling in the central nervous system. (C) 2008 Elsevier Inc. All rights reserved.