OpdA, a bacterial organophosphorus hydrolase, prevents lethality in rats after poisoning with highly toxic organophosphorus pesticides.
Organophosphorus (OP) pesticides poison more than 3,000,000 people every year in the developing world, mostly through intentional self-poisoning. Advances in medical therapy for OP poisoning have lagged, and current treatment is not highly effective with mortality of up to 40% in even the most advanced Western medical facilities. Administration of a broadly active bacterial OP hydrolase to patients in order to hydrolyze OPs in circulation might allow current therapies to be more effective. The objective of this work was to evaluate the efficacy of a new recombinant bacterial OP hydrolase (OpdA), cloned from Agrobacterium radiobacter, in rat models of two chemically distinct but highly toxic and rapidly acting OP pesticides: dichlorvos and parathion. Without OpdA treatment, median time to death in rats poisoned with 3x LD(50) of dichlorvos or parathion was 6 min and 25.5 min, respectively. Administration of a single dose of OpdA immediately after dichlorvos resulted in 100% survival at 24h, with no additional antidotal therapy. After parathion poisoning, OpdA alone caused only a delay to death. However, an additional two doses of OpdA resulted in 62.5% survival at 24 h after parathion poisoning. In combination with pralidoxime therapy, a single dose of OpdA increased survival to 75% after parathion poisoning. Our results demonstrate that OpdA is able to improve survival after poisoning by two chemically distinct and highly toxic OP pesticides.
Bird
Steven B
SB
Department of Emergency Medicine, Division of Toxicology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. birds@ummhc.org
Sutherland
Tara D
TD
Gresham
Chip
C
Oakeshott
John
J
Scott
Colin
C
Eddleston
Michael
M
D000818:Animals; D043303:Aryldialkylphosphatase / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000627:therapeutic use*; D004006:Dichlorvos / Q000506:poisoning*; D007306:Insecticides / Q000506:poisoning*; D008297:Male; D062025:Organophosphate Poisoning; D010278:Parathion / Q000506:poisoning*; D011220:Pralidoxime Compounds / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D001426:Bacterial Proteins; D007306:Insecticides; D011220:Pralidoxime Compounds; D010278:Parathion; D004006:Dichlorvos; D043303:Aryldialkylphosphatase; C028797:pralidoxime