Effect of cytochrome P450 1A induction on oxidative damage in rat brain

Polycyclic and halogenated aromatic hydrocarbons (PAHs and HAHs) can enhance the generation of reactive oxygen species (ROS) by inducing cytochrome P450 1A (CYP 1A) in vivo and in vitro. While the brain is vulnerable to oxidative injury, whether or not CYP 1A induction in the brain can produce measu...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2001-07, Vol.223 (1-2), p.89-94
Main Authors: Liu, L, Bridges, R J, Eyer, C L
Format: Article
Language:English
Subjects:
Animals
Antioxidants
Aromatic hydrocarbons
Biomarkers
Brain
Brain - drug effects
Brain - enzymology
Brain - metabolism
Cytochrome
Cytochrome P-450 CYP1A1 - biosynthesis
Cytochrome P-450 CYP1A1 - genetics
Cytochrome P-450 CYP1A1 - metabolism
Enzyme Induction
Gene Expression Regulation, Enzymologic - drug effects
Gene Expression Regulation, Enzymologic - physiology
Halogenated hydrocarbons
Isoenzymes - biosynthesis
Isoenzymes - genetics
Isoenzymes - metabolism
Liver - enzymology
Male
Methylcholanthrene - administration & dosage
Methylcholanthrene - pharmacology
Oxidation-Reduction
Oxidative Stress - physiology
Polycyclic aromatic hydrocarbons
Rats
Rats, Sprague-Dawley
Rodents
Thiobarbituric Acid Reactive Substances - metabolism
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Summary:Polycyclic and halogenated aromatic hydrocarbons (PAHs and HAHs) can enhance the generation of reactive oxygen species (ROS) by inducing cytochrome P450 1A (CYP 1A) in vivo and in vitro. While the brain is vulnerable to oxidative injury, whether or not CYP 1A induction in the brain can produce measurable levels of oxidative damage has not been reported. The objective of this study was to investigate the effect of this induction on oxidative damage to the CNS. Time course changes in rat brain CYP 1A activity were determined by measurement of ethoxyresorufin O-deethylase (EROD) activity in whole brain homogenates. Three days after exposure of rats to five daily injections of 3-methylcholanthrene (3-MC) an approximately sevenfold increase in EROD activity was observed. Hepatic levels were increased 60-100 fold. This increase in CYP 1A activity was not accompanied by increased protein or lipid oxidation as measured by tryptophan fluorescence and TBAR formation, or decreased glutamine synthetase (GS) activity. These findings indicate that if increased CYP 1A activity in the brain following 3-MC treatment leads to increased ROS generation, the increase is insufficient to overwhelm the endogenous antioxidant defense system, produce detectable oxidative damage, and alter glutamate homeostasis.
ISSN:0300-8177
1573-4919
DOI:10.1023/a:1017904912654