Species differences in the reactivation of organophosphate-inhibited plasma esterases by diacetylmonoxime.
A study was conducted to assess whether the protection afforded to organophosphatepoisoned animals by diacetylmonoxime (DAM) was correlated with the reactivation of non-essential aliesterases (AliE). In vitro, the DAM-catalyzed reactivation of plasma AliE and cholinesterases (psi ChE) of rat, rabbit and guinea pig inhibited by 10-5 M diisopropylphosphorofluoridate (DFP) and O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP) was investigated. Marked reactivation of the rat plasma enzymes was achieved with 10mM DAM. Higher concentrations (30 mM) were necessary for the slow reactivation of rabbit and guinea pig plasma AliE. Reactivation of the psiChE of these species was comparatively slow. Reactivation of DDVP-inhibited esterases proceeded in all species at a more rapid rate than those inhibited by DFP. The dependence of psiChE reactivation upon concomitant more rapid reactivation of AliE by DAM was demonstrated using Sephadex fractionated AliE and psiChE but only a marked effect was observed with the rat, suggesting that the plasma AliE of this species is functionally different. The in vitro observations were confirmed by in vivo studies in rats and rabbits. DAM (50 or 150 mg/kg), administered to atropinized rats 15 min before a lethal dose of DFP, protected the animals. Few severe toxic signs were observed and reactivation of both plasma AliE and psiChE occurred. In contrast, DAM protected the rabbit against a lethal dose of DFP but only reactivation of the erythrocyte acetylcholinesterase was observed.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002415:Cats; D002800:Cholinesterase Inhibitors; D002850:Chromatography, Gel; D004006:Dichlorvos / Q000494:pharmacology; D004950:Esterases / Q000037:antagonists & inhibitors* / Q000097:blood; D006168:Guinea Pigs; D006736:Horses; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology*; D008297:Male; D010091:Oximes / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D002800:Cholinesterase Inhibitors; D010091:Oximes; D007531:Isoflurophate; D001285:Atropine; D004006:Dichlorvos; D004950:Esterases