ANTAGONISM OF THE LETHAL EFFECTS OF PARAOXON BY CARRIER ERYTHROCYTES CONTAINING PHOSPHOTRIESTERASE

Annealed murine erythrocytes were employed as a carrier model to antag onize the toxic effects of organophosphorus agents, These resealed cel ls containing a recombinant phosphotriesterase provided striking prote ction against the lethal effect of paraoxon, an active metabolite of a n agricultural pesticide, parathion, Phosphotriesterase hydrolyzes par aoxon to the less-toxic 4-nitrophenol and diethylphosphate, This enzym e was encapsulated into carrier erythrocytes by hypotonic dialysis wit h subsequent resealing and annealing, These carrier cells were adminis tered to mice either alone or in combination with pralidoxime (2-PAM) and/or atropine, The recipient animals were subsequently challenged wi th paraoxon and a marked protection was noted, Protection of free enzy me and encapsulated enzyme was compared and the encapsulated enzyme wa s found to persist longer and possess much greater efficacy, Less seru m cholinesterase inhibition also was observed with this enhanced prote ction. These results indicate that the erythrocyte carrier alone is qu ite effective in the antagonism of organophosphorus intoxication. More over, when these carrier cells were administered in combination with 2 -PAM and/or atropine, a marked synergism was observed. (C) 1995 Societ y of Toxicology