Antagonism of the Lethal Effects of Paraoxon by Carrier Erythrocytes Containing Phosphotriesterase

• Published in: Fundamental and applied toxicology Vol. 28; no. 2; pp. 209 - 214
• Main Authors: Pei, L., Petrokivocs, I., Way, J.L.
• Format: Journal Article
• Language: English
• Published: Boston, MA Elsevier Science (USA) 01.12.1995; San Diego, CA Academic Press; New York, NY
• Subjects: ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; ADDITIF; ADITIVOS; Animals; ANTAGONISME; ANTAGONISMO; Antidotes - therapeutic use; Aryldialkylphosphatase; ATROPINA; ATROPINE; Atropine - pharmacology; Biological and medical sciences; CHOLINESTERASE; Cholinesterases - blood; Cholinesterases - metabolism; COLINESTERASA; COMPOSE ORGANOPHOSPHORE; COMPUESTO ORGANICO DEL FOSFORO; Dose-Response Relationship, Drug; Drug Carriers; Drug Combinations; ENCAPSULACION; ENCAPSULATION; ENVENENAMIENTO; ERITROCITOS; ERYTHROCYTE; Erythrocytes - physiology; ESTERASAS; ESTERASE; Esterases - metabolism; Esterases - pharmacology; INHIBICION; INHIBITION; Insecticides - antagonists & inhibitors; Insecticides - toxicity; INTOXICATION; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mortality; OXIMAS; OXIME; Paraoxon - antagonists & inhibitors; Paraoxon - toxicity; PESTICIDE; Pesticides, fertilizers and other agrochemicals toxicology; PLAGUICIDAS; PLASMA SANGUIN; PLASMA SANGUINEO; Pralidoxime Compounds - pharmacology; RATON; SOURIS; Survival; Time Factors; TOXICIDAD; TOXICITE; Toxicology; Encapsulation; Drug combination; Enzyme; Rodentia; Pesticides; Red blood cell; Esterases; Hydrolysis; Phosphoric triester hydrolases; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Hydrolases; Poisoning; Organophosphorus compounds; Aryldialkylphosphatase; Antidote
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1006/faat.1995.1161

Antagonism of the Lethal Effects of Paraoxon by Carrier Erythrocytes Containing Phosphotriesterase. Pei, L., Petrikovics, I., and Way, J. L. (1995). Fundam. Appl. Taxicol. 28, 209-214. Annealed murine erythrocytes were employed as a carrier model to antagonize the toxic effects of organophosphorus agents. These resealed cells containing a recombinant phosphotriesterase provided striking protection against the lethal effect of paraoxon, an active metabolite of an agricultural pesticide, parathion. Phosphotriesterase hydrolyzes paraoxon to the less-toxic 4-nitrophenol and diethylphosphate. This enzyme was encapsulated into carrier erythrocytes by hypotonic dialysis with subsequent resealing and annealing. These carrier cells were administered to mice either alone or in combination with pralidoxime (2-PAM) and/or atropine. The recipient animals were subsequently challenged with paraoxon and a marked protection was noted. Protection of free enzyme and encapsulated enzyme was compared and the encapsulated enzyme was found to persist longer and possess much greater efficacy, Less serum cholinesterase inhibition also was observed with this enhanced protection. These results indicate that the erythrocyte carrier alone is quite effective in the antagonism of organophosphorus intoxication. Moreover, when these carrier cells were administered in combination with 2-PAM and/or atropine, a marked synergism was observed.