Paraoxon has only a minimal effect on pralidoxime brain concentration in rats

George A. Petroianu, D. E. Lorke, M. Y. Hasan, A. Adem, R. Sheen, S. M. Nurulain, H. Kalász

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Clinical experience with oximes, cholinesterase reactivators used in organophosphorus poisoning, has been disappointing. Their major anatomic site of therapeutic action and their ability to pass the blood-brain barrier (BBB) are controversial. Although their physico-chemical properties do not favour BBB penetration, access of oximes to the brain may be facilitated by organophosphates. The effect of the organophosphate paraoxon (POX) on pralidoxime (2-PAM) brain entry was therefore determined. Rats either received 50 μmol 2-PAM only (G1) or additionally 1 μmol POX (≈ LD75) (G2). Three animals each were killed after 5, 15, 30, 60, 90, 120, 180, 240, 360, 480 min, and 2-PAM concentrations in the brain and plasma were measured using HPLC. Moreover, the effect of brain perfusion with isotonic saline on subsequent 2-PAM measurements was assessed. The maximal 2-PAM concentration (Cmax) in G1 brain was 6% of plasma Cmax, while in G2 brains it was 8%. Similarly, the ratio of the area under the curve (AUC) brain to plasma was 8% in G1 and 12% in G2. Brain tmax (15 min) was slightly higher than plasma tmax (5 min). The AUC of plasma 2-PAM did not differ between G1 and G2. However, in G1, AUC brain was significantly lower than in G2, the differences probably being clinically irrelevant. In perfused brains, 2-PAM concentrations were very close to those of non-perfused brains. The results indicate that brain penetration of 2-PAM is poor and that organophosphates only have a modest effect on 2-PAM BBB penetration. Brain perfusion does not significantly alter 2-PAM measurements and is therefore considered unnecessary.

Original languageEnglish
Pages (from-to)350-357
Number of pages8
JournalJournal of Applied Toxicology
Volume27
Issue number4
DOIs
Publication statusPublished - Jul 2007

Fingerprint

Paraoxon
Rats
Brain
Organophosphates
Plasmas
Blood-Brain Barrier
Area Under Curve
Oximes
pralidoxime
Cholinesterase Reactivators
Perfusion
Organophosphate Poisoning
Chemical properties

Keywords

  • Blood-brain barrier
  • HPLC
  • Organophosphate
  • Oxime
  • Paraoxon
  • Pralidoxime

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Petroianu, G. A., Lorke, D. E., Hasan, M. Y., Adem, A., Sheen, R., Nurulain, S. M., & Kalász, H. (2007). Paraoxon has only a minimal effect on pralidoxime brain concentration in rats. Journal of Applied Toxicology, 27(4), 350-357. https://doi.org/10.1002/jat.1213

Paraoxon has only a minimal effect on pralidoxime brain concentration in rats. / Petroianu, George A.; Lorke, D. E.; Hasan, M. Y.; Adem, A.; Sheen, R.; Nurulain, S. M.; Kalász, H.

In: Journal of Applied Toxicology, Vol. 27, No. 4, 07.2007, p. 350-357.

Research output: Contribution to journalArticle

Petroianu, GA, Lorke, DE, Hasan, MY, Adem, A, Sheen, R, Nurulain, SM & Kalász, H 2007, 'Paraoxon has only a minimal effect on pralidoxime brain concentration in rats', Journal of Applied Toxicology, vol. 27, no. 4, pp. 350-357. https://doi.org/10.1002/jat.1213
Petroianu GA, Lorke DE, Hasan MY, Adem A, Sheen R, Nurulain SM et al. Paraoxon has only a minimal effect on pralidoxime brain concentration in rats. Journal of Applied Toxicology. 2007 Jul;27(4):350-357. https://doi.org/10.1002/jat.1213
Petroianu, George A. ; Lorke, D. E. ; Hasan, M. Y. ; Adem, A. ; Sheen, R. ; Nurulain, S. M. ; Kalász, H. / Paraoxon has only a minimal effect on pralidoxime brain concentration in rats. In: Journal of Applied Toxicology. 2007 ; Vol. 27, No. 4. pp. 350-357.
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