Abdominal bloating and irritable bowel syndrome like symptoms following microinstillation inhalation exposure to chemical warfare nerve agent VX in guinea pigs
Abdominal bloating and irritable bowel syndrome like symptoms following microinstillation inhalation exposure to chemical warfare nerve agent VX in guinea pigs
复制标题
豚鼠微滴吸入接触化学战神经毒剂 VX 后出现腹胀和肠易激综合征等症状
DOI：
10.1177/0748233707081720
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发表时间：
2007
影响因子：
1.9
通讯作者：
M. Nambiar
中科院分区：
文献类型：
--
作者：
Alexandre M. Katos;Michele L. Conti;T. S. Moran;R. K. Gordon;B. P. Doctor;A. Sciuto;M. Nambiar
在评价甲基硫代膦酸S-(2-(二(1-甲乙基)氨基)乙基)O-乙酯(VX)的呼吸毒性和肺损伤的治疗方法时，我们观察到动物腹部出现异常肿胀。众所周知，神经毒剂会增加唾液、鼻腔和胃肠道的分泌物，并导致腹泻。这项研究是为了研究VX对胃肠道(GI)的影响，因为腹部病理可能会影响呼吸，并导致持续的呼吸系统毒性。分别于染毒前、染毒后27.3 mg/m~3，每隔30min至染毒后2小时，用微量滴注法测量左下腹部大小和中腹直径。VX暴露组和生理盐水暴露组大鼠上腹部周长均有下降，但VX暴露组上腹部周长下降幅度略大于VX暴露组，但在暴露后60~90min，VX暴露组小鼠腰围略有增加，但与生理盐水对照组相似。左下腹部靠近盲肠，在胸骨末端下方6 cm处和右侧2 cm处，30~60min时增大，90~120min时显著增大。此外，与对照组相比，接触VX的动物表现出松散的粪便。24小时的尸检显示VX暴露动物的小肠扭转运动增强。体内组织AChE测定显示，VX暴露动物的食道和肠道有较高的抑制作用，这表明微量滴注VX后，相当数量的药物被定位于GI。这些结果表明，微量滴注吸入VX可引起类似于肠易激综合征和腹胀的胃肠功能紊乱。
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 30min intervals up to 2h 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 90min post-VX exposure but was similar to saline controls. The lower left abdomen near to the cecum, 6 cm below and 2 cm 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 24 h 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 microinstillation inhalation VX exposure induces gastrointestinal disturbances similar to that of irritable bowel syndrome and bloating.