Lorke_2014_J.Appl.Toxicol_34_1096

Reference

Title : Prophylactic administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone - Lorke_2014_J.Appl.Toxicol_34_1096
Author(s) : Lorke DE , Nurulain SM , Hasan MY , Kuca K , Petroianu GA
Ref : J Appl Toxicol , 34 :1096 , 2014
Abstract :

Poisoning with organophosphorus compounds (OPCs) poses a serious threat worldwide. OPC-induced mortality can be significantly reduced by prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors. The only American Food and Drug Administration (FDA)-approved substance for such pre-treatment (to soman exposure) is presently pyridostigmine, although its efficacy is controversial. In search for more efficacious and broad-spectrum alternatives, we have assessed in vivo the mortality-reducing efficacy of a group of five compounds with known AChE inhibitory activity (pyridostigmine, physostigmine, ranitidine, tacrine and K-27), when given in equitoxic dosage (25% of LD01 ) 30 min before exposure to the OPC terbufos sulfone. Protection was quantified in rats by determining the relative risk of death (RR) using Cox analysis, with RR = 1 for animals given only terbufos sulfone, but no pre-treatment. All tested AChE inhibitors reduced terbufos sulfone-induced mortality significantly (p </= 0.05) as compared with the non-treatment group (RR = 1: terbufos sulfone only). Best in vivo protection from terbufos sulfone-induced mortality was achieved, when K-27 was given before terbufos sulfone exposure (RR = 0.06), which was significantly (P </= 0.05) superior to the pre-treatment with all other tested compounds, for example tacrine (RR = 0.21), pyridostigmine (RR = 0.28), physostigmine (RR = 0.29) and ranitidine (RR = 0.33). The differences in efficacy between tacrine, pyridostigmine, physostigmine and ranitidine were not statistically significant. Prophylactic administration of an oxime (such as K-27) in case of imminent OPC exposure may be a viable option. Copyright (c) 2013 John Wiley & Sons, Ltd.

PubMedSearch : Lorke_2014_J.Appl.Toxicol_34_1096
PubMedID: 24136594

Related information

Inhibitor Terbufos

Citations formats

Lorke DE, Nurulain SM, Hasan MY, Kuca K, Petroianu GA (2014)
Prophylactic administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone
J Appl Toxicol 34 :1096

Lorke DE, Nurulain SM, Hasan MY, Kuca K, Petroianu GA (2014)
J Appl Toxicol 34 :1096