STUDIES ON THE MECHANISM OF PHENOBARBITAL-INDUCED PROTECTION AGAINST PARATHION IN ADULT FEMALE RATS

¹ Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada

Phenobarbital affords significant protection against parathion toxicity in adult female rats. The effect of phenobarbital on the in vitro and in vivo metabolism of parathion was therefore investigated. The activity of the enzyme systems involved in the metabolism of parathion was measured in various tissues of control and phenobarbital-treated animals. In both groups it was found that the insecticide was metabolized predominatly by the liver. After pretreatment with phenobarbital, the liver parathion oxidase activity was increased approximately 5-fold; the liver paraoxonase activity, 1.5-fold; and the combined oxidase and paraoxonase activities, 3-fold. Phenobarbital had little effect on serum paraoxonase activity. Under in vitro conditions, the rate of formation of diethyl phosphoric acid and diethyl phosphorothioic acid by liver homogenates was increased by 5.4-fold and 9.2-fold, respectively, in the phenobarbital-treated group. Analysis of the urinary metabolites of parathion indicated that phenobarbital-treated rats excreted larger amounts of diethyl phosphorothioic acid but smaller amounts of diethyl phosphoric acid over a period of nine hours after parathion, the difference being especially pronounced during the first two-hour period. These results suggest that in the intact animal phenobarbital stimulates only the direct degradation of parathion to diethyl phosphorothioic acid and p-nitrophenol.

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