STUDIES ON THE MECHANISM OF PHENOBARBITAL-INDUCED PROTECTION AGAINST MALATHION AND EPN

Abstract

The administration of phenobarbital, at a dose of 50 mg/kg per day, increased the resistance of adult female rats to the toxic effects of malathion and EPN, as measured by an increase in the LD50 and a decrease in the in vivo anticholinesterase activity of the thiophosphates. Maximum protection against EPN occurred after a pretreatment period of 2 days with phenobarbital whereas maximum protection against malathion was achieved after five successive daily administrations of phenobarbital. The administration of phenobarbital also resulted in a rise in the liver ali-esterase activity as evidenced by an increased ability of liver homogenates to hydrolyze methyl butyrate. Administration of tri-o-cresyl phosphate (TOCP), an ali-esterase inhibitor, at a dose of 100 mg/kg, abolished the protective effect of phenobarbital against malathion but did not change the effect against EPN. It is concluded that the induction of liver ali-esterases plays a major role in the protection afforded by phenobarbital against malathion, but that ali-esterases have little to do regarding the protection against EPN.