Shih T M, Penetar D M, McDonough J H, Romano J A, King J M
Pharmacology Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Brain Res Bull. 1990 Mar;24(3):429-36. doi: 10.1016/0361-9230(90)90097-j.
The toxicity (lethality, acute toxic signs and body weight loss) of the irreversible ChE inhibitor soman was assessed in four groups of male rats differing in age: 30, 60, 120 and 240 days old. Plasma and brain regional ChE activity profiles were also studied in these groups. All measures of the toxicity of soman were found to increase with age. The calculated 24-hr LD50s were 110, 87, 66 and 59 micrograms/kg, IM, for 30-, 60-, 120- and 240-day-old rats, respectively. A significant and positive age-related effect on toxic sign rating scores was observed at one hr following soman injection. Furthermore, during a 14-day postsoman observation period, it was observed that young rats had less initial weight loss and more rapid, sustained recovery of growth than older animals. Survivors from the two oldest age groups did not recover to baseline body weights by the end of the 14-day observation period. Basal level of plasma ChE activity did not change significantly with age, while brain regional ChE showed two distinct age-dependent patterns: a linear decrease in the brainstem, midbrain and cerebellum and an inverted U-shaped change in the cortex, hippocampus and striatum. Our data suggest a relationship between soman toxicity and the aging process, but fails to demonstrate a definite relationship between soman toxicity and basal ChE activity in blood and brain of rats.
在四组不同年龄(30、60、120和240日龄)的雄性大鼠中评估了不可逆性胆碱酯酶(ChE)抑制剂梭曼的毒性(致死率、急性中毒体征和体重减轻情况)。还研究了这些组大鼠血浆和脑区的ChE活性谱。结果发现,梭曼毒性的所有指标均随年龄增长而增加。30、60、120和240日龄大鼠经肌肉注射梭曼后,计算得出的24小时半数致死剂量(LD50)分别为110、87、66和59微克/千克。注射梭曼1小时后,观察到中毒体征评分存在显著的与年龄相关的正向效应。此外,在梭曼注射后的14天观察期内,发现幼鼠初始体重减轻较少,且生长恢复比老年动物更快、更持久。两个年龄最大组的存活大鼠在14天观察期结束时未恢复到基线体重。血浆ChE活性的基础水平并未随年龄显著变化,而脑区ChE呈现出两种不同的年龄依赖性模式:脑干、中脑和小脑呈线性下降,而皮层、海马体和纹状体呈倒U形变化。我们的数据表明梭曼毒性与衰老过程之间存在关联,但未能证明梭曼毒性与大鼠血液和脑中基础ChE活性之间存在明确关系。