EFFECT OF PHENOBARBITAL AND BETA-NAPHTHOFLAVONE ON ACTIVITIES OF DIFFERENCE RAT ESTERASES AFTER PARAOXON EXPOSURE

1. The effects of two model inducers of the cytochrome P450 system, ph enobarbital (PB) and beta-naphthoflavone (NF), on the toxicity of para oxon were studied in rats. 2. Paraoxon toxicity was measured by inhibi tion of brain acetylcholinesterase (AChE) activity. 3. PB treatment di d not affect the toxicity of paraoxon, whereas NF increased the inhibi tion of brain AChE, PB administration slightly increased the activitie s of some peripheral cholinesterases and carboxylesterases, as well as liver microsomal paraoxonase (Pxase). 4. NF administration, in contra st, decreased the activities of peripheral esterases. Serum Pxase acti vity was reduced by both inducers. 5. Hepatic CYP2B and CYP1A were mar kedly induced by PB and NF, respectively. 6. Cytochrome P450 isoenzyme s induced by PB or NF seemed not to be critical in the detoxification of paraoxon in vivo, NF caused a general reduction of peripheral ester ases, which led to an increase in paraoxon toxicity. 7. The results in dicated the great importance of peripheral cholinesterases and carboxy lesterases as a detoxifying mechanism of paraoxon. The role of serum p araoxonase was not critical. (C) 1998 Elsevier Science Inc.