Effect of phenobarbital and beta-naphthoflavone on activities of different rat esterases after paraoxon exposure.
1. The effects of two model inducers of the cytochrome P450 system, phenobarbital (PB) and beta-naphthoflavone (NF), on the toxicity of paraoxon were studied in rats. 2. Paraoxon toxicity was measured by inhibition of brain acetylcholinesterase (AChE) activity. 3. PB treatment did not affect the toxicity of paraoxon, whereas NF increased the inhibition of brain AChE. PB administration slightly increased the activities of some peripheral cholinesterases and carboxylesterases, as well as liver microsomal paraoxonase (Pxase). 4. NF administration, in contrast, decreased the activities of peripheral esterases. Serum Pxase activity was reduced by both inducers. 5. Hepatic CYP2B and CYP1A were markedly induced by PB and NF, respectively. 6. Cytochrome P450 isoenzymes induced by PB or NF seemed not to be critical in the detoxification of paraoxon in vivo. NF caused a general reduction of peripheral esterases, which led to an increase in paraoxon toxicity. 7. The results indicated the great importance of peripheral cholinesterases and carboxylesterases as a detoxifying mechanism of paraoxon. The role of serum paraoxonase was not critical.
Kaliste-Korhonen
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E
National Laboratory Animal Center, University of Kuopio, Finland. eila.kalistekorhonen@uki.fi
Tuovinen
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K
Hänninen
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O
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction; D004950:Esterases / Q000096:biosynthesis*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D010261:Paraoxon / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D004950:Esterases; D010261:Paraoxon; D010634:Phenobarbital