Robinson C P, Smith P W, Crane C R, McConnell J K, Allen L V, Endecott B R
Arch Int Pharmacodyn Ther. 1978 Jan;231(1):168-76.
Pretreatment of rats with 10 mg of ethylestrenol (17alpha-ethylestr-4-en-17beta-ol) by force feeding twice daily for three days and once on the fourth day decreased the severity of parathion (0,0-diethyl 0-4-nitrophenyl phosphorothioate) toxicity and caused a 150% increase in the parathion LD50 in male animals. It decreased by 51% cholinesterase inhibition in the brain caused by i.p. injection of 2 mg of parathion/kg body weight but not that of an equitoxic dose (0.5 mg/kg) of its active metabolite, paraoxon (0,0-diethyl 0-4-nitrophenyl phosphate). It decreased by 29% cholinesterase inhibition in plasma following i.p. administration of parathion but caused only a 16% decrease in cholinesterase inhibition following administration of the equitoxic dose of paraoxon. It did not protect against brain cholinesterase inhibition by 4 mg/kg of parathion given i.v.; however, brain parathion levels were 16% lower in rats pretreated with ethylestrenol than in control rats. It increased the rate of inactivation of both parathion and paraoxon by liver microsomal enzyme preparations. Thus enzyme induction seems to account for the protection afforded by ethylestrenol to toxicity following poisoning by organophosphates.
对大鼠每日两次强制灌胃10毫克乙基雌烯醇（17α - 乙基 - 4 - 烯 - 17β - 醇），持续三天，第四天灌胃一次，可降低对硫磷（0,0 - 二乙基 - 0 - 4 - 硝基苯基硫代磷酸酯）的毒性严重程度，并使雄性动物的对硫磷半数致死量增加150%。腹腔注射2毫克/千克体重的对硫磷所引起的脑内胆碱酯酶抑制作用降低了51%，但对其等毒性剂量（0.5毫克/千克）的活性代谢产物对氧磷（0,0 - 二乙基 - 0 - 4 - 硝基苯基磷酸酯）所引起的脑内胆碱酯酶抑制作用则无此效果。腹腔注射对硫磷后，血浆中的胆碱酯酶抑制作用降低了29%，但给予等毒性剂量的对氧磷后，胆碱酯酶抑制作用仅降低了16%。静脉注射4毫克/千克的对硫磷时，它不能防止脑胆碱酯酶受到抑制；然而，用乙基雌烯醇预处理的大鼠脑内对硫磷水平比对照大鼠低16%。它提高了肝微粒体制剂对对硫磷和对氧磷的失活速率。因此，酶诱导似乎可以解释乙基雌烯醇对有机磷中毒毒性的保护作用。
