Assessing Protection Against OP Pesticides and Nerve Agents Provided by Wild-Type HuPON1 Purified from Trichoplusia ni Larvae or Induced via Adenoviral Infection

Human paraoxonase-1 (HuPON1) has been proposed as a catalytic bioscavenger of organophosphorus (OP) pesticides and nerve agents. We assessed the potential of this enzyme to protect against OP poisoning using two different paradigms. First, recombinant HuPON1 purified from cabbage loopers (iPON1; Tri...

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Bibliographic Details
Main Authors: Hodgins, Sean M, Kasten, Shane A, Harrison, Joshua, Otto, Tamara C, Oliver, Zeke P, Rezk, Peter, Reeves, Tony E, Chilukuri, Nageswararao, Cerasoli, Douglas M
Format: Report
Language:English
Subjects:
ADENOVIRUSES
Agricultural Chemistry
CATALYTIC BIOSCAVENGERS
GUINEA PIGS
HUPON1(HUMAN PARAOXONASE 1)
IN VIVO ANALYSIS
IN VIVO EFFICACY
LARVAE
LETHAL DOSAGE
METABOLITES
MICE
NERVE AGENTS
OP(ORGANOPHOSPHORUS)
Organic Chemistry
ORGANOPHOSPHATES
PESTICIDES
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Summary:Human paraoxonase-1 (HuPON1) has been proposed as a catalytic bioscavenger of organophosphorus (OP) pesticides and nerve agents. We assessed the potential of this enzyme to protect against OP poisoning using two different paradigms. First, recombinant HuPON1 purified from cabbage loopers (iPON1; Trichoplusia ni) was administered to guinea pigs, followed by exposure to at least 2 times the median lethal dose (LD50) of the OP nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF), or chlorpyrifos oxon, the toxic metabolite of the OP pesticide chlorpyrifos. In the second model, mice were infected with an adenovirus that induced expression of HuPON1 and then exposed to sequential doses of GD, VX, or (as reported previously) diazoxon, the toxic metabolite of the OP pesticide diazinon. In both animal models, the exogenously added HuPON1 protected animals against otherwise lethal doses of the OP pesticides but not against the nerve agents. Together, the results support prior modeling and in vitro activity data which suggest that wild-type HuPON1 does not have sufficient catalytic activity to provide in vivo protection against nerve agents. The original document contains color images. Published in Chemico-Biological Interactions, v203 p177 180, 2013.