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.

Post-exposure therapy with recombinant human BuChE following percutaneous VX challenge in guinea-pigs

“…Intussusception is a consequence of nerve agent poisoning that has been previously reported following acute soman intoxication (Wetherell et al, 2007) and has also been observed in previous studies following VX poisoning via the percutaneous route (Mumford et al, 2011) and via microinstillation (Katos et al, 2007). Full intussusception was observed in two saline-treated guinea-pigs, and a further two animals had changes in the gastrointestinal tract consistent with the initial stages of intussusception; one further animal had abnormal changes in the lower GI tract which were not judged to be the start of intussusception.…”

Post-exposure therapy with human butyrylcholinesterase following percutaneous VX challenge in guinea pigs

“…This has previously been reported following soman poisoning in guinea pigs 16 and after VX poisoning via the percutaneous route 11 or via microinstillation. 27 In the current study, the absence of any therapeutic drugs that could alleviate this, e.g. atropine or other antimuscarinic compounds, might have exacerbated the development of this condition.…”

Toxicity assessment of perovskite nanocomposites: In vivo study

“…Rats exposed to perovskite demonstrated back-arching, abdomen destination, and testes enlargement. Back-arching induction in rodents may indicate activity reduction while abdominal destination might have resulted from spinal cord injury induced by the perovskite dose (Gondim et al, 2003; Katos et al, 2007). In addition, the treated rats showed significant decrease in the average body weight gain that might be related to the impact of perovskite on the oxidative metabolic enzymes (Aniagu et al, 2005).…”