Bioscavenger for protection from toxicity of organophosphorus compounds.
Current antidotal regimens for organophosphorus compound (OP) poisoning consist of a combination of pretreatment with a spontaneously reactivating AChE inhibitor such as pyridostigmine bromide, and postexposure therapy with anticholinergic drugs such as atropine sulfate and oximes such as 2-PAM chloride (Gray, 1984). Although these antidotal regimens are effective in preventing lethality of animals from OP poisoning, they do not prevent postexposure incapacitation, convulsions, performance deficits, or, in many cases, permanent brain damage (Dunn and Sidell, 1989). These problems stimulated the development of enzyme bioscavengers as a pretreatment to sequester highly toxic OPs before they reach their physiological targets. Several studies over the last two decades have demonstrated that exogenously administered human serum butyrylcholinesterase (Hu BChE) can be used successfully as a safe, efficacious, and single prophylactic treatment to counteract the toxicity of OPs. It also has potential use for first responders (civilians) reacting to terrorist nerve gas release, pesticide overexposure, or succinylcholine-induced apnea. A dose of 200 mg of Hu BChE in humans is envisioned as a prophylactic treatment that can protect from exposure of 2-5 x LD50 of nerve agents (Ashani, 2000).
Saxena
Ashima
A
Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. ashima.saxena@amedd.army.mil
Sun
Wei
W
Luo
Chunyuan
C
Myers
Todd M
TM
Koplovitz
Irwin
I
Lenz
David E
DE
Doctor
Bhupendra P
BP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000992:Antitoxins / Q000494:pharmacology*; D002091:Butyrylcholinesterase / Q000097:blood* / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005612:Freeze Drying; D006801:Humans; D008253:Macaca mulatta; D010755:Organophosphates / Q000633:toxicity*; D012377:Rodentia; D012449:Safety
D000975:Antioxidants; D000992:Antitoxins; D016166:Free Radical Scavengers; D010755:Organophosphates; D002091:Butyrylcholinesterase