[Changes in plasma endotoxin content due to cholinesterase inhibitor VX intoxication and therapeutic effect of benthiaczine in mice].
OBJECTIVE
To investigate the therapeutic effect and its mechanisms of benthiaczine on cholinesterase inhibitor VX poisoning by observing on the changes in plasma endotoxin content in mice.


METHODS
Three hundred and six male Kunming mice were randomly assigned to five groups: normal group, VX poisoning (model) group, benthiaczine, atropine or 654-2 pretreatment group. The above mentioned drugs were respectively given 10 minutes before hypodermic injection of VX in a dose of 0.02 mg/kg. The plasma concentration of endotoxin was measured at 1.5, 3, 6, 24, 48 and 72 hours after VX poisoning.


RESULTS
After VX injection, the endotoxin concentration in model group was significantly increased compared with normal group (all P < 0.01). The endotoxin concentration in model group was (5.36+/-1.62) kEU/L at 1.5 hours, which was almost twice of that of normal group [(1.90+/-0.41) kEU/L]. It increased gradually to (11.47+/-3.90) kEU/L at 24 hours, which was 5 fold of that of the normal group (all P < 0.01), and it maintained on the abnormally high level until 48 hours, then declined to the level of normal group after 72 hours. The endotoxin concentration of benthiaczine pretreatment group was significantly lower than that of model group at 1.5 hours and 3 hours after VX injection [(3.73+/-0.71) kEU/L, (3.95+/-1.26) kEU/L, respectively, P < 0.01 and P < 0.05], but there was no significant difference between two groups at 6 hours [(8.77+/-1.85) kEU/L] and 24 hours [(11.47+/-2.51) kEU/L], though it was significantly higher than normal group (both P < 0.01). It lowered to the normal level at 48 hours. The endotoxin concentration in atropine pretreatment group was significantly higher than model group at 1.5-24 hours after VX injection (P < 0.05 or P < 0.01), while that of 654-2 pretreatment group reached a peak at 6 hours, which was significantly higher than that of the model group (P < 0.01).


CONCLUSIONS
The increased endotoxin concentration induced by VX in mice 1.5-48 hours after poisoning can be reversed by pretreatment of benthiaczine, but aggravated by pretreatment of atropine or 654-2. The administration of benthiaczine could alleviate the injury to the gut barrier function thus delay translocation of endotoxin into blood, and also shorten the time of endotoxemia.
Song
Li-xue
LX
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
Tang
Yuan
Y
Wang
Hai
H
D000818:Animals; D001285:Atropine / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood / Q000188:drug therapy*; D004731:Endotoxins / Q000097:blood*; D008297:Male; D051379:Mice; D011897:Random Allocation
D002800:Cholinesterase Inhibitors; D004731:Endotoxins; D001285:Atropine