Gastrointestinal acetylcholinesterase activity following endotracheal microinstillation inhalation exposure to sarin in guinea pigs.
The goal of this study was to assess acetylcholinesterase (AChE) inhibition at different regions of the gastrointestinal (GI) tract following inhalation exposure to nerve agent sarin. Seven major regions of the GI tract were removed from saline control animals (n=3) and 677.4 mg/m(3) sarin-exposed animals at 4h (n=4) and 24h (n=4) post-exposure. AChE activity was determined in blood and homogenized tissue supernatant by specific Ellman's assay using Iso-OMPA, a BChE inhibitor, and expressed as activity/optical density of hemoglobin for blood and activity/mg protein for tissues. Our data showed that the AChE activity was significantly decreased for groups both 4h and 24h post-sarin exposure. Among the seven chosen regions of the guinea pig GI tract, duodenum showed the highest AChE activity in control animals. The AChE activity was significantly decreased in the stomach (p=0.03), duodenum (p=0.029), jejunum (p=0.006), and ileum (p=0.006) 4h following sarin exposure. At 24h post-sarin exposure the AChE activity of duodenum (p=0.029) and ileum (p=0.006) was significantly inhibited. Esophagus showed no inhibition following sarin exposure at both 4h and 24h groups. These results suggest that the AChE activity is different in different regions of the GI tract and highest levels of AChE inhibition following sarin exposure were seen in regions exhibiting higher overall AChE activity and cholinergic function.
Chanda
Soma
S
Division of Brain Dysfunction and Blast Injury, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Song
Jian
J
Rezk
Peter
P
Sabnekar
Praveena
P
Doctor
Bhupendra P
BP
Sciuto
Alfred M
AM
Nambiar
Madhusoodana P
MP
D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism*; D000280:Administration, Inhalation; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000201:enzymology*; D006168:Guinea Pigs; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D008297:Male; D012524:Sarin / Q000008:administration & dosage* / Q000633:toxicity*
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D012524:Sarin; D000110:Acetylcholinesterase