title: Treatment with endotracheal therapeutics after sarin microinstillation inhalation exposure increases blood cholinesterase levels in guinea pigs.
abstract: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in the blood and tissues of animals that are treated with a number of endotracheally aerosolized therapeutics for protection against inhalation toxicity to sarin. Therapeutics included, aerosolized atropine methyl bromide (AMB), scopolamine or combination of AMB with salbutamol, sphingosine 1-phosphate, keratinocyte growth factor, adenosine A1 receptor antisense oligonucleotide (EPI2010), 2,3-diacetyloxybenzoic acid (2,3 DABA), oxycyte, and survanta. Guinea pigs exposed to 677.4 mg/m(3) or 846.5 mg/m(3) (1.2 LCt(50)) sarin for 4 min using a microinstillation inhalation exposure technique and treated 1 min later with the aerosolized therapeutics. Treatment with all therapeutics significantly increased the survival rate with no convulsions throughout the 24 h study period. Blood AChE activity determined using acetylthiocholine as substrate showed 20% activity remaining in sarin-exposed animals compare to controls. In aerosolized AMB and scopolamine-treated animals the remaining AChE activity was significantly higher (45-60%) compared to sarin-exposed animals (p < 0.05). Similarly, treatment with all the combination therapeutics resulted in significant increase in blood AChE activity in comparison to sarin-exposed animals although the increases varied between treatments (p < 0.05). BChE activity was increased after treatment with aerosolized therapeutics but was lesser in magnitude compared to AChE activity changes. Various tissues showed elevated AChE activity after therapeutic treatment of sarin-exposed animals. Increased AChE and BChE activities in animals treated with nasal therapeutics suggest that enhanced breathing and reduced respiratory toxicity/lung injury possibly contribute to rapid normalization of chemical warfare nerve agent inhibited cholinesterases.
authors.affiliation: Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Magnus M
authors.initials: MM
authors.lastname: Che
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.forename: Samuel
authors.initials: S
authors.lastname: Oguntayo
authors.forename: Bhupendra P
authors.initials: BP
authors.lastname: Doctor
authors.forename: Peter
authors.initials: P
authors.lastname: Rezk
authors.forename: Michael W
authors.initials: MW
authors.lastname: Perkins
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Sciuto
authors.forename: Madhusoodana P
authors.initials: MP
authors.lastname: Nambiar
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002091:Butyrylcholinesterase / Q000097:blood / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced / Q000201:enzymology; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D012138:Respiratory Therapy; D012524:Sarin / Q000633:toxicity*
chemical_list: D000931:Antidotes; D001993:Bronchodilator Agents; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D012524:Sarin; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase