Age-Related Changes in Cholinesterase Activity and Soman Toxicity in the Rat

摘要

Plasma and brain regional cholinesterase (ChE) activity profiles and the toxicity (lethality, acute toxic signs and body weight loss) of the irreversible ChE inhibitor soman (pinacolyl methylphosphonofluoridate) were assessed in four groups of male rats differing in age: 30, 60, 120 and 240 days old. Plasma ChE did not change significantly with age. Brain regional ChE activity showed two distinct age-dependent patterns: a linear decrease in the brainstem, midbrain and cerebellum and an inverterted U-shaped change in the cortex, hippocampus and was found to increase with age. The calculated 24-hr LD50s were 110.0, 87.2, 66.1 and 48.6 microgram/kilogram, 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 post-soman observation period, it was observed that young rats displayed a Less severe initial weight loss and had a more rapid, sustained recovery of growth, while order animals tended to lose a greater absolute amount of weight and had slower recoveries. Survivors from the two oldest age groups did not recover to baseline body weights by the end of the 14-day observation period. These data suggest a possible relationship between soman toxicity and the age-related changes of ChE in certain brain areas.