title: Acute renal failure enhances the antidotal activity of pralidoxime towards paraoxon-induced respiratory toxicity.
abstract: We recently showed in a rat model of dichromate-induced acute renal failure (ARF) that the elimination but not the distribution of pralidoxime was altered resulting in sustained plasma pralidoxime concentrations. The aim of this study was to compare the efficiency of pralidoxime in normal and acute renal failure rats against paraoxon-induced respiratory toxicity. Ventilation at rest was assessed using whole-body plethysmography after subcutaneous administration of either saline or paraoxon (50% of the LD(50)), in the control and ARF rats. Thirty minutes after administration of paraoxon, either saline or 50mg/kg of pralidoxime was administered intramuscularly. ARF had no significant effects on the ventilation at rest. The effects of paraoxon on respiration were not significantly different in the control and ARF group. Paraoxon increased the total time (T(TOT)), expiratory time (T(E)) and tidal volume (V(T)), and decreased the respiratory frequency (f). In paraoxon-poisoned rats with normal renal function, pralidoxime had a significant but transient effect regarding the T(TOT) and V(T) (p<0.05). In the ARF group, the same dose of pralidoxime significantly decreased the T(TOT), T(E), and V(T) and increased f during 90 min (p<0.01). In conclusion, pralidoxime had partial and transient effects towards paraoxon-induced respiratory toxicity in control rats; and a complete and sustained correction in ARF rats.
authors.affiliation: University Paris Descartes, Neuropsychopharmacologie des addictions, CNRS, UMR7157, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Kayouka
authors.forename: Pascal
authors.initials: P
authors.lastname: Houzé
authors.forename: Marcel
authors.initials: M
authors.lastname: Debray
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Baud
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood*; D000818:Animals; D000931:Antidotes / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007306:Insecticides / Q000506:poisoning*; D007928:Lethal Dose 50; D008297:Male; D010261:Paraoxon / Q000506:poisoning*; D010993:Plethysmography, Whole Body; D011220:Pralidoxime Compounds / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D012120:Respiration Disorders / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000931:Antidotes; D007306:Insecticides; D011220:Pralidoxime Compounds; C028797:pralidoxime; D010261:Paraoxon