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© 1989 Oxford University Press

research-article

Hormone- and Dose Schedule-Dependent Protection by HI-6 against Soman and Tabun Poisoning

PAUL M LUNDY, JEAN CHRISTOPHE GOULET and BRIAN T HAND

Biomedical Defence Section, Defence Research Establishment Suffield Ralston, Alberta, Canada

Received June 13, 1988; accepted October 17, 1988

Hormone- and Dose Schedule-Dependent Protection by HI-6 against Soman and Tabun Poisoning. LUNDY, P. M., Gourzr, J. C., AND HAND, B. T. (1989). Fundam. Appl. Toxicol. 12, 595–603. The protective ratio produced by HI-6 (with atropinc) 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 atropinc), 1 mm 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. It can be inferred from the results that for maximal effectiveness against soman or tabun, maintenance of adequate blood/tissue levels of HI-6 is absolutely essential.


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