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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hodgins, Sean M. Kasten, Shane A. Harrison, Joshua Otto, Tamara C. Oliver, Zeke P. Rezk, Peter Reeves, Tony E. Chilukuri, Nageswararao Cerasoli, Douglas M. |
| Description | Country affiliation: United States Author Affiliation: Hodgins SM ( Physiology and Immunology Branch, Research Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, United States.) |
| Abstract | 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 (LD(50)) 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. |
| File Format | HTM / HTML |
| ISSN | 00092797 |
| Issue Number | 1 |
| Volume Number | 203 |
| e-ISSN | 18727786 |
| Journal | Chemico-Biological Interactions |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-03-25 |
| Publisher Place | Ireland |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Biochemistry Discipline Pharmacology Aryldialkylphosphatase Administration & Dosage Chemical Warfare Agents Toxicity Organophosphorus Compounds Pesticides Animals Antidotes Pharmacokinetics Genetics Isolation & Purification Chlorpyrifos Analogs & Derivatives Guinea Pigs Humans Male Mice Moths Organophosphates Recombinant Proteins Sarin Soman Journal Article Research Support, U.s. Gov't, Non-p.h.s. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Toxicology |
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