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Effect of pyridostigmine, pralidoxime and their combination on survival and cholinesterase activity in rats exposed to the organophosphate paraoxon

  • Toxicity and Mechanisms
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Abstract

Pyridostigmine (PSTG) is a carbamate inhibitor of cholinesterases. Carbamates are known to confer some protection from the lethal effects of (some) organophosphorus compounds. Recently, based on animal data, the FDA approved oral PSTG for pre-exposure treatment of soman. The purpose of the study was to quantify in vivo the effect of PSTG pre-treatment on survival in rats exposed to the organophosphate paraoxon (POX) with and without subsequent reactivator (pralidoxime) treatment. POX is a highly toxic non-neuropathic ethyl organophospate. Pralidoxime (PRX) is the enzyme reactivator used by some NATO armies. The prospective, controlled animal (rat) study included Group 1 that received 1 μmol POX (≈LD75); Group 2 that received 1 μmol PSTG followed 30 min later by 1 μmol POX; Group 3 that received 1 μmol PSTG followed 30 min later by 1 μmol POX and 50 μmol PRX; Group 4 that received 1 μmol POX and 50 μmol PRX; Group 5 that received 1 μmol PSTG; Group 6 that received 50 μmol PRX and Group 7 that received 1 μmol PSTG followed 30 min later by 50 μmol PRX. Each group contained six rats. The experiment was repeated twelve times (12 cycles). All substances were applied i.p. From surviving animals of eight cycles tail blood was taken for red blood cell acetylcholinesterase (RBC-AChE) measurements. The animals were monitored for 48 h and mortality (survival time) was recorded. RBC-AChE activities were determined. Mortality was analysed using Kaplan–Meier plots. Both PSTG and PRX statistically significantly decreased organophosphate induced mortality in the described model. While the same applies to their combination the decrease in mortality when using both PSTG and PRX is less than that achieved with their single use (but not significantly so). While certainly further work using different organophosphorus compounds and animal species are needed before a final conclusion is reached, the animal data presented does not support the combined use of PSTG and PRX.

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Acknowledgments

This work was supported by individual university grant # 01-04-8-11/04 from the United Arab Emirates University (UAEU).

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  1. Faculty of Medicine and Health Sciences, Department of Pharmacology and Therapeutics, United Arab Emirates University, P.O.Box 17 666, Al Ain, United Arab Emirates

    Georg A. Petroianu, Syed M. Nurulain, Kholoud Arafat, Sheen Rajan & Mohammed Y. Hasan

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  1. Georg A. Petroianu
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  2. Syed M. Nurulain
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  3. Kholoud Arafat
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  4. Sheen Rajan
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  5. Mohammed Y. Hasan
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Correspondence to Georg A. Petroianu.

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Petroianu, G.A., Nurulain, S.M., Arafat, K. et al. Effect of pyridostigmine, pralidoxime and their combination on survival and cholinesterase activity in rats exposed to the organophosphate paraoxon . Arch Toxicol 80, 777–784 (2006). https://doi.org/10.1007/s00204-006-0098-9

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