The toxicity of soman in the African green monkey (Chlorocebus aethiops)

The toxicity of soman in the African green monkey (Chlorocebus aethiops)
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DOI:
10.1080/15376510600972733
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发表时间:
2007-01-01
影响因子:
3.2
通讯作者:
Evans, Jackie
Evans, Jackie
中科院分区:
医学4区
文献类型:
--
作者:
Despain, Kenneth E.;McDonough, John H.;Evans, Jackie

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这项研究确定了梭曼对非洲绿猴(ChlorOcean Bus Atheiop)的毒性,是探索该物种作为神经毒剂研究模型的适用性的第一步。通过手术向雄性非洲绿猴植入遥测设备,以监测脑电(EEG)和心电(CG)活动。于不同时间取血检测全血乙酰胆碱酯酶(AChE)活性和心肌肌钙蛋白I(CTnI)。血AChE活性在接触梭曼后6h为0.0%~2.5%,30d恢复到31.9%~72.0%。暴露后6h的cTnI水平变化范围为0.64~6.55 ng/mL,提示心脏损伤。梭曼用生理盐水配制,浓度为100微克/毫升。采用小样本的自上而下设计,受试者分别接触5.01、6.31或7.94g/kg梭曼肌注。第一组给予5.01g/kg梭曼肌注,存活下来。3名受试者注射6.31g/kg梭曼肌注后存活。3名受试者接受7.94g/kg梭曼肌注,在25分钟、26分钟或6小时内死亡。所有受试者在2-7分钟内出现肌肉痉挛、震颤、咀嚼和大量唾液的中毒体征。强直-阵挛运动痉挛和EEG发作在震颤开始后2-18分钟开始。结果表明,梭曼对非洲绿猴的48hIM LD50为7.15g/kg。非洲绿猴体内梭曼中毒的迹象和速度与恒河猴、食蟹猴和狒狒中描述的一致。
This study determines soman toxicity in African green monkeys (Chlorocebus aethiops) and is the first step in exploring the suitability of this species as a model for nerve agent studies. Male African green monkeys were surgically implanted with telemetry devices to monitor electroencephalographic (EEG) and electrocardiographic (ECG) activity. Blood was taken at various times to measure whole blood acetylcholinesterase (AChE) activity and cardiac troponin I (cTnI). Blood AChE activity relative to baseline was 0.0% to 2.5% 6 h after soman exposure and recovered to 31.9% to 72.0% by 30 days after exposure. The 6 h postexposure cTnI levels varied from 0.64 to 6.55 ng/mL, suggesting cardiac damage. Soman was prepared in saline to a concentration of 100 mu g/mL. Using an up-down design for small samples, subjects were exposed to 5.01, 6.31, or 7.94 g/kg soman IM. The first subject was given 5.01 g/kg soman IM and survived. Three subjects received 6.31 g/kg soman IM and survived. Three subjects received 7.94 g/kg soman IM and died within 25 min, 26 min, or 6 h. In all subjects, toxic signs of muscle fasciculation, tremors, chewing, and profuse salivation developed within 2 to 7 min. Tonic-clonic motor convulsions and EEG seizure began between 2 and 18 min after tremor onset. The 48 h IM LD50 of soman in saline in the African green monkey was calculated to be 7.15 g/kg. The signs and speed of soman intoxication in African green monkeys were consistent with those described in rhesus, cynomolguscynomolgus, and baboons.