Phenobarbital induces monkey brain CYP2E1 protein but not hepatic CYP2E1, in vitro or in vivo chlorzoxazone metabolism

Anna M. Lee, Meenal Joshi, Jiang Yue, Rachel F. Tyndale

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Cytochrome P450 2E1 (CYP2E1) is expressed in the brain and liver, and can metabolize clinical drugs and activate toxins. The effect of phenobarbital on hepatic and brain CYP2E1 is unclear. We investigated the effect of chronic phenobarbital treatment on in vivo chlorzoxazone disposition (a CYP2E1 probe drug), in vitro chlorzoxazone metabolism, and hepatic and brain CYP2E1 protein levels in African Green monkeys (Cercopithecus aethiops). Monkeys were given oral saccharine or saccharine supplemented with 20 mg/kg phenobarbital (N = 6/group) for 22 days. Phenobarbital did not induce in vivo chlorzoxazone disposition, in vitro chlorzoxazone metabolism or hepatic CYP2E1 protein levels (all P > 0.05). However, phenobarbital induced brain CYP2E1 protein levels, using immunoblotting, by 1.26-fold in the cerebellum (P = 0.01) and 1.46-fold in the putamen (P = 0.04). Phenobarbital also increased cell-specific CYP2E1 expression, for example in the frontal cortical pyramidal neurons and cerebellar Purkinje cells. This data indicates that phenobarbital does not alter hepatic metabolism, but may alter metabolism of CYP2E1 substrates within the brain.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalEuropean Journal of Pharmacology
Volume552
Issue number1-3
DOIs
StatePublished - Dec 15 2006

Fingerprint

Chlorzoxazone
Cytochrome P-450 CYP2E1
Phenobarbital
Haplorhini
Liver
Brain
Proteins
Cercopithecus aethiops
In Vitro Techniques
Pyramidal Cells
Purkinje Cells
Putamen
Immunoblotting
Pharmaceutical Preparations
Cerebellum

Keywords

  • (Monkey)
  • Brain
  • CYP2E1
  • Chlorzoxazone
  • Phenobarbital
  • Protein induction

Cite this

Phenobarbital induces monkey brain CYP2E1 protein but not hepatic CYP2E1, in vitro or in vivo chlorzoxazone metabolism. / Lee, Anna M.; Joshi, Meenal; Yue, Jiang; Tyndale, Rachel F.

In: European Journal of Pharmacology, Vol. 552, No. 1-3, 15.12.2006, p. 151-158.

Research output: Contribution to journalArticle

@article{bb5fc2b74b5e4ee7bc94eb66f76a75bb,
title = "Phenobarbital induces monkey brain CYP2E1 protein but not hepatic CYP2E1, in vitro or in vivo chlorzoxazone metabolism",
abstract = "Cytochrome P450 2E1 (CYP2E1) is expressed in the brain and liver, and can metabolize clinical drugs and activate toxins. The effect of phenobarbital on hepatic and brain CYP2E1 is unclear. We investigated the effect of chronic phenobarbital treatment on in vivo chlorzoxazone disposition (a CYP2E1 probe drug), in vitro chlorzoxazone metabolism, and hepatic and brain CYP2E1 protein levels in African Green monkeys (Cercopithecus aethiops). Monkeys were given oral saccharine or saccharine supplemented with 20 mg/kg phenobarbital (N = 6/group) for 22 days. Phenobarbital did not induce in vivo chlorzoxazone disposition, in vitro chlorzoxazone metabolism or hepatic CYP2E1 protein levels (all P > 0.05). However, phenobarbital induced brain CYP2E1 protein levels, using immunoblotting, by 1.26-fold in the cerebellum (P = 0.01) and 1.46-fold in the putamen (P = 0.04). Phenobarbital also increased cell-specific CYP2E1 expression, for example in the frontal cortical pyramidal neurons and cerebellar Purkinje cells. This data indicates that phenobarbital does not alter hepatic metabolism, but may alter metabolism of CYP2E1 substrates within the brain.",
keywords = "(Monkey), Brain, CYP2E1, Chlorzoxazone, Phenobarbital, Protein induction",
author = "Lee, {Anna M.} and Meenal Joshi and Jiang Yue and Tyndale, {Rachel F.}",
year = "2006",
month = "12",
day = "15",
doi = "10.1016/j.ejphar.2006.09.006",
language = "English (US)",
volume = "552",
pages = "151--158",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Phenobarbital induces monkey brain CYP2E1 protein but not hepatic CYP2E1, in vitro or in vivo chlorzoxazone metabolism

AU - Lee, Anna M.

AU - Joshi, Meenal

AU - Yue, Jiang

AU - Tyndale, Rachel F.

PY - 2006/12/15

Y1 - 2006/12/15

N2 - Cytochrome P450 2E1 (CYP2E1) is expressed in the brain and liver, and can metabolize clinical drugs and activate toxins. The effect of phenobarbital on hepatic and brain CYP2E1 is unclear. We investigated the effect of chronic phenobarbital treatment on in vivo chlorzoxazone disposition (a CYP2E1 probe drug), in vitro chlorzoxazone metabolism, and hepatic and brain CYP2E1 protein levels in African Green monkeys (Cercopithecus aethiops). Monkeys were given oral saccharine or saccharine supplemented with 20 mg/kg phenobarbital (N = 6/group) for 22 days. Phenobarbital did not induce in vivo chlorzoxazone disposition, in vitro chlorzoxazone metabolism or hepatic CYP2E1 protein levels (all P > 0.05). However, phenobarbital induced brain CYP2E1 protein levels, using immunoblotting, by 1.26-fold in the cerebellum (P = 0.01) and 1.46-fold in the putamen (P = 0.04). Phenobarbital also increased cell-specific CYP2E1 expression, for example in the frontal cortical pyramidal neurons and cerebellar Purkinje cells. This data indicates that phenobarbital does not alter hepatic metabolism, but may alter metabolism of CYP2E1 substrates within the brain.

AB - Cytochrome P450 2E1 (CYP2E1) is expressed in the brain and liver, and can metabolize clinical drugs and activate toxins. The effect of phenobarbital on hepatic and brain CYP2E1 is unclear. We investigated the effect of chronic phenobarbital treatment on in vivo chlorzoxazone disposition (a CYP2E1 probe drug), in vitro chlorzoxazone metabolism, and hepatic and brain CYP2E1 protein levels in African Green monkeys (Cercopithecus aethiops). Monkeys were given oral saccharine or saccharine supplemented with 20 mg/kg phenobarbital (N = 6/group) for 22 days. Phenobarbital did not induce in vivo chlorzoxazone disposition, in vitro chlorzoxazone metabolism or hepatic CYP2E1 protein levels (all P > 0.05). However, phenobarbital induced brain CYP2E1 protein levels, using immunoblotting, by 1.26-fold in the cerebellum (P = 0.01) and 1.46-fold in the putamen (P = 0.04). Phenobarbital also increased cell-specific CYP2E1 expression, for example in the frontal cortical pyramidal neurons and cerebellar Purkinje cells. This data indicates that phenobarbital does not alter hepatic metabolism, but may alter metabolism of CYP2E1 substrates within the brain.

KW - (Monkey)

KW - Brain

KW - CYP2E1

KW - Chlorzoxazone

KW - Phenobarbital

KW - Protein induction

UR - http://www.scopus.com/inward/record.url?scp=33750471638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750471638&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2006.09.006

DO - 10.1016/j.ejphar.2006.09.006

M3 - Article

C2 - 17049344

AN - SCOPUS:33750471638

VL - 552

SP - 151

EP - 158

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-3

ER -