Abstract
Phosphorothionate insecticides and their active oxon metabolites can be detoxified by a variety of hepatic mechanisms. Cytochrome P450-mediated dearylation activity was higher in males than in females. While dearylation was induced by phenobarbital in both sexes, it was induced by beta-naphthoflavone in females only. Detoxication of oxons in the presence of EDTA was inducible by phenobarbital, was higher in males than in females, and paralleled aliesterase activity. In vitro Ca(++)-dependent A-esterase-mediated hydrolysis of chlorpyrifos-oxon but not of paraoxon occurred at biologically relevant nM concentrations. This hydrolysis was also inducible by phenobarbital. Glutathione-mediated conjugation did not appear to be relevant to the disposition of the phosphorothionates studied here. Hepatic detoxication via dearylation, aliesterase phosphorylation and A-esterase-mediated hydrolysis (for some organophosphates) all appear to be relevant reactions in the attenuation of acute toxicity.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholinesterase / metabolism*
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Animals
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Benzoflavones / pharmacology
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Calcium / metabolism
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Carboxylesterase
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Carboxylic Ester Hydrolases / metabolism
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Cerebral Cortex / drug effects
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Cerebral Cortex / enzymology
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Chlorpyrifos / metabolism*
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Chlorpyrifos / toxicity*
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Cytochrome P-450 Enzyme System / metabolism
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Edetic Acid / pharmacology
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Female
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Glutathione / metabolism
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Inactivation, Metabolic
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Male
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Medulla Oblongata / drug effects
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Medulla Oblongata / enzymology
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Microsomes, Liver / drug effects
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Microsomes, Liver / enzymology
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Paraoxon / metabolism
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Paraoxon / toxicity
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Parathion / metabolism*
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Parathion / toxicity*
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Phenobarbital / pharmacology
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Rats
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Rats, Sprague-Dawley
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Sex Factors
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beta-Naphthoflavone
Substances
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Benzoflavones
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beta-Naphthoflavone
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Parathion
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Cytochrome P-450 Enzyme System
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Edetic Acid
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arginine esterase
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Carboxylic Ester Hydrolases
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Carboxylesterase
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Acetylcholinesterase
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Glutathione
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Chlorpyrifos
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Paraoxon
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Calcium
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Phenobarbital