Age-related differences in soman toxicity and in blood and brain regional cholinesterase activity.
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.
Shih
T M
TM
Pharmacology Division, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Penetar
D M
DM
McDonough
J H
JH
Romano
J A
JA
King
J M
JM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002802:Cholinesterases / Q000378:metabolism*; D007928:Lethal Dose 50; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D012999:Soman / Q000633:toxicity*
D002800:Cholinesterase Inhibitors; D012999:Soman; D002802:Cholinesterases