Picrotoxin as a potent inducer of rat hepatic cytochrome P450, CYP2b1 and CYP2b2

Hydeyuki Yamada, Hiroshi Fujisaki, Hayato Kaneko, Yuji Ishii, Tomoyuki Hamaguchi, Kazuta Oguri

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22 Citations (Scopus)


The induction by the central stimulant picrotoxin of hepatic drug-metabolizing enzymes was studied in rats. The hepatic content of P450 and the activity of benzphetamine N-demethylation increased gradually after administration of picrotoxin dissolved in drinking water (2 mg/mL), to three-times higher levels than the initial values at the third day of treatment. The increase in benzphetamine N-demethylase activity by picrotoxin was somewhat higher than the increase produced by phenobarbital. Supporting these results, immunoblot analysis showed that CYP2B1 and 2B2 proteins in the liver microsomes were increased by picrotoxin. Picrotoxinin and picrotin, which are components of the picrotoxin molecule, had the same ability to induce the hepatic activity of benzphetamine N-demethylation. The liver microsomal activities of testosterone 16β- and 16β-hydroxylation were enhanced significantly after treatment with picrotoxinin and picrotin. However, benzo[a]pyrene 3-hydroxylation, aniline 4-hydroxylation, and testosterone hydroxylations at the 2α- and 7α-positions were not increased by picrotoxinin and picrotin treatment. In addition to monooxygenase, significant induction of glutathione S-transferase activity for 1-chloro-2,4-dinitrobenzene and UDP-glucuronyltransferase activity for 4-hydroxybiphenyl and 4-nitrophenol was also observed by pretreatment of picrotoxin. These results clearly indicate that picrotoxin is an inducer of phenobarbital-inducible liver enzymes.

Original languageEnglish
Pages (from-to)1783-1789
Number of pages7
JournalBiochemical Pharmacology
Issue number9
Publication statusPublished - May 5 1993

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology


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