Effects of HI 6, diazepam and atropine on soman-induced IL-1 beta protein in rat brain.
The current treatment for soman-intoxication is the oxime HI 6 together with the anticholinergic drug atropine. This antidote combination is known to have effects on seizures, respiratory system, blood pressure and animal survival in experiments. However, the inflammatory responses following soman-intoxication leading to neuronal damage have not been fully evaluated. In this paper we focus on the cytokine IL-1beta induction in the rat brain after soman-intoxication (1.0 x LD50 and 1.1 x LD50) and during antidote treatment. We analyzed the IL-1beta levels in rat brain to determine the effects of time of antidote HI 6 and atropine; the effects of different combinations of HI 6 and atropine; and also the effects of antidotes diazepam and atropine following soman-intoxication. We observed that the initiation of the antidote combination of HI 6 and atropine following soman-intoxication was crucial for successful treatment. The study also demonstrated that atropine alone was more effective against IL-1beta up-regulation after soman-intoxication within the 2-h time frame, than the combination of the HI 6 and atropine, the therapy of choice in many countries. Furthermore, treatment with a combination of diazepam and atropine maintained IL-1beta levels at normal when administered at the onset of the seizures following soman exposure. Soman-intoxicated groups without seizures did not have an elevated cytokine level. This corroborates our earlier studies where soman-intoxicated animals with seizures had high levels of IL-1beta, while animals without seizures had normal values. Our results show that both time and the antidote regime are crucial to the success of treatment.
Svensson
I
I
Swedish Defence Research Agency, Division of NBC Defence, SE-901 82 Umeå, Sweden. indra.svensson@foi.se
Waara
L
L
Cassel
G
G
D000818:Animals; D001285:Atropine / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis*; D008297:Male; D010091:Oximes; D011726:Pyridinium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D012999:Soman / Q000633:toxicity*
D007375:Interleukin-1; D010091:Oximes; D011726:Pyridinium Compounds; D001285:Atropine; D012999:Soman; C022870:asoxime chloride; D003975:Diazepam