Sean M Hodgins

Publications (2)12.14 Total impact

• Article: Assessing Protection against OP Pesticides and Nerve Agents Provided by Wild-Type HuPON1 Purified from Trichoplusia ni Larvae or Induced via Adenoviral Infection.

  Sean M Hodgins, Shane A Kasten, Joshua Harrison, Tamara C Otto, Zeke P Oliver, Peter Rezk, Tony E Reeves, Nageswararao Chilukuri, Douglas M Cerasoli
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  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.
  Chemico-biological interactions 11/2012; · 2.46 Impact Factor
• Source

  Available from: pnas.org

  Article: Plant-derived human butyrylcholinesterase, but not an organophosphorous-compound hydrolyzing variant thereof, protects rodents against nerve agents.

  Brian C Geyer, Latha Kannan, Pierre-Emmanuel Garnaud, Clarence A Broomfield, C Linn Cadieux, Irene Cherni, Sean M Hodgins, Shane A Kasten, Karli Kelley, Jacquelyn Kilbourne, Zeke P Oliver, Tamara C Otto, Ian Puffenberger, Tony E Reeves, Neil Robbins, Ryan R Woods, Hermona Soreq, David E Lenz, Douglas M Cerasoli, Tsafrir S Mor
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  ABSTRACT: The concept of using cholinesterase bioscavengers for prophylaxis against organophosphorous nerve agents and pesticides has progressed from the bench to clinical trial. However, the supply of the native human proteins is either limited (e.g., plasma-derived butyrylcholinesterase and erythrocytic acetylcholinesterase) or nonexisting (synaptic acetylcholinesterase). Here we identify a unique form of recombinant human butyrylcholinesterase that mimics the native enzyme assembly into tetramers; this form provides extended effective pharmacokinetics that is significantly enhanced by polyethylene glycol conjugation. We further demonstrate that this enzyme (but not a G117H/E197Q organophosphorus acid anhydride hydrolase catalytic variant) can prevent morbidity and mortality associated with organophosphorous nerve agent and pesticide exposure of animal subjects of two model species.
  Proceedings of the National Academy of Sciences 11/2010; 107(47):20251-6. · 9.68 Impact Factor