The protective effects of ethylestrenol against acute poisoning by organophosphorus cholinesterase inhibitors in rats.
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.
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000506:poisoning*; D005032:Ethylestrenol / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010261:Paraoxon / Q000378:metabolism / Q000494:pharmacology / Q000506:poisoning*; D010278:Parathion / Q000378:metabolism / Q000494:pharmacology / Q000506:poisoning*; D051381:Rats
D002800:Cholinesterase Inhibitors; D010278:Parathion; D005032:Ethylestrenol; D010261:Paraoxon