title: Abdominal bloating and irritable bowel syndrome like symptoms following microinstillation inhalation exposure to chemical warfare nerve agent VX in guinea pigs.
abstract: While assessing the methylphosphonothioic acid S-(2-(bis(1-methylethyl)amino)ethyl)O-ethyl ester (VX) induced respiratory toxicity and evaluating therapeutics against lung injury, we observed that the animals were experiencing abnormal swelling in the abdominal area. Nerve agent has been known to increase salivary, nasal and gastrointestinal secretion and cause diarrhea. This study was initiated to investigate the effect of VX on the gastrointestinal tract (GI) since abdominal pathology may affect breathing and contribute to the on going respiratory toxicity. The mid-abdominal diameter and the size of the lower left abdomen was measured before and after 27.3 mg/m3 VX exposure by microinstillation and at 30 min intervals up to 2 h post-VX exposure. Both VX and saline exposed animals exhibited a decrease in circumference of the upper abdomen, although the decrease was slightly higher in VX-exposed animals up to 1 h. The waist diameter increased slightly in VX-exposed animals from 60 to 90 min post-VX exposure but was similar to saline controls. The lower left abdomen near to the cecum, 6 cm below and 2cm to the right of the end of the sternum, showed an increase in size at 30-60 min that was significantly increased at 90-120 min post-VX exposure. In addition, VX-exposed animals showed loose fecal matter compared to controls. Necropsy at 24h showed an increased small intestine twisting motility in VX-exposed animals. Body tissue AChE assay showed high inhibition in the esophagus and intestine in VX-exposed animals indicating that a significant amount of the agent is localized to the GI following microinstillation exposure. These results suggest that microinstillatipn inhalation VX exposure induces gastrointestinal disturbances similar to that of irritable bowel syndrome and bloating.
authors.affiliation: Department of Biochemical Pharmacology, Division of Biochemistry, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA.
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Katos
authors.forename: Michele L
authors.initials: ML
authors.lastname: Conti
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Moran
authors.forename: Richard K
authors.initials: RK
authors.lastname: Gordon
authors.forename: Bhupendra P
authors.initials: BP
authors.lastname: Doctor
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Sciuto
authors.forename: Madhusoodana P
authors.initials: MP
authors.lastname: Nambiar
mesh_terms: D000005:Abdomen / Q000473:pathology*; D000110:Acetylcholinesterase / Q000493:pharmacokinetics; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003967:Diarrhea / Q000139:chemically induced*; D004947:Esophagus / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010100:Oxygen / Q000097:blood
chemical_list: D000110:Acetylcholinesterase; D002619:Chemical Warfare Agents; D009946:Organothiophosphorus Compounds; D010100:Oxygen; C009680:VX-agent