DMD Celsis microsomes mean better data

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on January 24, 2006; DOI: 10.1124/dmd.105.008029

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.105.008029v1
34/4/647    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Joshi, M.
Right arrow Articles by Tyndale, R. F
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Joshi, M.
Right arrow Articles by Tyndale, R. F


Received for publication October 28, 2005.
Revised January 13, 2006.
Accepted for publication January 13, 2006.

Induction and Recovery Time Course of Rat Brain CYP2E1 following Nicotine treatment

Meenal Joshi 1* Rachel F Tyndale 1

1 University of Toronto

* Address correspondence to: E-mail: m.joshi{at}utoronto.ca

Abstract

CYP2E1, the primary ethanol-metabolizing cytochrome P450, metabolizes endogenous substrates (e.g. arachidonic acid), drugs (e.g. acetaminophen, chlorzoxazone) and bioactivates procarcinogens (e.g. tobacco-specific nitrosamines) and toxins (e.g. carbon tetrachloride). Nicotine from tobacco smoke may contribute to the enhanced hepatic CYP2E1 activity in smokers. We have previously shown that chronic nicotine treatment can increase CYP2E1 in rat liver and brain. Currently, induction of brain CYP2E1 was assessed following a single acute or a 7-day chronic treatment with saline or nicotine (1 mg/kg s.c.) with sacrifice performed at various times after the last injection. Chronic 7-day nicotine treatment showed highest levels of CYP2E1 12 h after the last injection in frontal cortex (1.4-fold, p<0.05) versus 8 h in hippocampus (1.8-fold, p<0.01) and cerebellum (1.4-fold, p<0.05), returning to basal levels by 24 h. In contrast, acute nicotine treatment did not induce CYP2E1 in frontal cortex and hippocampus but increased CYP2E1 in cerebellum 8 h post-treatment (1.6-fold, p<0.01). Brain CYP2E1 mRNA levels did not increase after chronic nicotine treatment suggesting non-transcriptional regulation. Thus, humans exposed to nicotine may have altered CYP2E1-mediated metabolism of centrally acting drugs and toxins as well as altered toxicity due to oxidative stress caused by CYP2E1. Those affected may include current and passive smokers and people that may be treated with nicotine such as smokers and potentially, patients with Alzheimer's, Parkinson's disease or ulcerative colitis.


Key words: CYP expression, CYP gene regulation, CYP induction, CYP2E, extrahepatic cytochrome P450, induction, neurotoxicity


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
F. J. Gonzalez
CYP2E1
Drug Metab. Dispos., January 1, 2007; 35(1): 1 - 8.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2006 by the American Society for Pharmacology and Experimental Therapeutics.