Item – Theses Canada

OCLC number
56329210
Link(s) to full text
LAC copy
LAC copy
Author
Micu, Alina L.(Alina Lucia),1975-
Title
An investigation of the induction of hepatic CYP2E1 by low doses of nicotine in the rat.
Degree
M. Sc. -- University of Toronto, 2003
Publisher
Ottawa :National Library of Canada = Bibliothèque nationale du Canada,[2004]
Description
1 microfiche.
Notes
Includes bibliographical references.
Abstract
CYP2E1 is an ethanol and drug-metabolizing enzyme that can also bioactivate hepatotoxins and procarcinogens and generate reactive oxygen species; it has been implicated in the pathogenesis of liver diseases and cancer. Cigarette smoke increases CYP2E1 activity in rodents and in humans, and we have shown that nicotine increases CYP2E1 protein and activity in the rat liver. In the current studies we have shown that the induction peaks at 4 hours post nicotine treatment and requires multiple exposures to nicotine. We have found that CYP2E1 is induced by very low doses of nicotine with an ED50 of 0.01 mg/kg s.c. Our mechanistic studies indicate that nicotine does not regulate CYP2E1 expression by transcriptional mechanisms or by protein stabilization. Cotinine, the main nicotine metabolite is not involved in CYP2E1 induction in our rat model. Our findings indicate that nicotine may increase CYP2E1-induced toxicity in smokers, passive smokers and people treated with nicotine.
ISBN
0612785718
9780612785717