Hormone- and dose schedule-dependent protection by HI-6 against soman and tabun poisoning.

Abstract

The protective ratio produced by HI-6 (with atropine) against soman and tabun poisoning in rats and guinea pigs was determined. The amount of protection afforded by HI-6 decreased with time following poisoning, prompting us to examine the effects of repeated doses of HI-6 (four additional) given over a 5-hr period. In addition, it was determined that HI-6 produced much better protection in female rats than male rats, which led to a study of the hormone dependence of this activity. When in addition to the first dose of HI-6 four additional doses were given over a 5-hr period, the protective ratio, defined as LD50 in treated animals/LD50 in untreated animals, in males against soman, increased from 4.2 to 7.8, and against tabun, from 2.5 to 6.6. A single dose of HI-6 produced a protective ratio in females of 10.5 against soman and 4.3 against tabun, whereas multiple doses increased these values to greater than 27 and 22, respectively. A regimen consisting of gonad removal and long-term treatment with a sex hormone of the opposite gender reversed the sex-related differences in response to the protective effects of HI-6. In addition a single injection of HI-6 (plus atropine), 1 min following either soman or tabun, produced good protective ratios in guinea pigs against both soman (between 4 and 5) and tabun (5.1); however, there was no apparent hormone-dependent effect similar to that obtained in rats. The results demonstrate unequivocal protective effects of HI-6 against tabun and a very dramatic hormone-dependent factor in its activity against either organophosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: P M Lundy, J C Goulet, B T Hand
• Journal: Fundamental and applied toxicology : official journal of the Society of Toxicology (Fundam Appl Toxicol) Vol. 12 Issue 3 Pg. 595-603 (Apr 1989) ISSN: 0272-0590 [Print] United States
• PMID: 2659414 (Publication Type: Journal Article)

Chemical References

• Cholinesterase Inhibitors
• Cholinesterase Reactivators
• Organophosphates
• Organophosphorus Compounds
• Oximes
• Pyridinium Compounds
• Obidoxime Chloride
• Testosterone
• Soman
• asoxime chloride
• tabun

Topics

• Animals
• Body Weight (drug effects)
• Cholinesterase Inhibitors (toxicity)
• Cholinesterase Reactivators (administration & dosage, pharmacology)
• Female
• Guinea Pigs
• Lethal Dose 50
• Male
• Obidoxime Chloride (pharmacology)
• Orchiectomy
• Organophosphates (antagonists & inhibitors, toxicity)
• Organophosphorus Compounds (antagonists & inhibitors)
• Ovariectomy
• Oximes
• Pyridinium Compounds (administration & dosage, pharmacology)
• Rats
• Rats, Inbred Strains
• Soman (antagonists & inhibitors, toxicity)
• Species Specificity
• Testosterone (blood)
• Time Factors