Effect of hepatic enzyme inducers on the in vivo and in vitro metabolism of dicrotophos,dimethoate, and phosphamidon in mice |
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| Authors: | Yueh-chu L Tseng Robert E Menzer |
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| Institution: | Department of Entomology, University of Maryland, College Park, Maryland 20742 USA |
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| Abstract: | Daily 75 mg/kg phenobarbital ip injections for 3 days or 25 ppm dieldrin in the diet of mice for 14 days caused an increase in liver cytochrome P-450 and blood B-esterase. Liver A-esterase was not significantly increased. Under in vitro conditions, phenobarbital and dieldrin induced the oxidative as well as hydrolytic metabolism of dicrotophos, dimethoate, and phosphamidon by liver homogenates or combined microsomes plus 105,000g supernatant fractions. The concentration of dimethoxon was increased more than fourfold by the pretreatments after incubation for 4 hr at 37.5°C with NADPH added. The organophosphorus insecticides used in this study were not metabolized as well by the liver microsomes alone or 105,000g supernatant alone, as by the combination of microsomes and 105,000g supernatant. Under in vivo conditions in mice, phenobarbital and dieldrin treatments increased the urinary recovery of metabolites in the initial 6 hr after 14C]carbonyl-dimethoate or 14C]N-ethyl-phosphamidon administration. Analysis of urine showed that the inducers caused a more than sixfold increase in dimethoxon recovered and twofold increase in water-soluble nontoxic metabolites within 6 hr after dimethoate administration. With phosphamidon both inducers increased the rate of metabolism, and the total recovery in aqueous and chloroform fractions was decreased. These results suggest that increased dimethoate toxicity after phenobarbital and dieldrin treatments in whole animals results from stimulation of the activation of dimethoate to dimethoxon, while the increase in hydrolytic products after both pretreatments results in decreased toxicity of the direct acetylcholinesterase inhibitors, dicrotophos and phosphamidon. |
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