Year: 1998
Type: dissertation
Abstract: Polycyclic and halogenated aromatic hydrocarbons (PAHs and HAHs) are widespread and persistent environmental contaminants.Most of their toxicological effects are mediated through activation of the aryl hydrocarbon receptor (AhR), which leads to transcriptional activation of cytochrome P-450 lA l and 1A2 (CYP lA l/2) genes.Induction of CYP lA l/2 increases drug metabolism and enhances the generation of reactive oxygen species (ROS) in vivo.Oxidative stress is an important mediator of various neurological and hepatic disorders.In the brain, oxidative damage can alter key components of glutamate homeostasis, such as glutamine synthetase (GS).This change can generate abnormally elevated extracellular glutamate, and lead to excitotoxicity.PAHs and HAHs have been shown to induce CYP lA l in rat brain.However, whether the induction of CYP lA l can cause oxidative damage or interact with other pathologies in the central nervous system has not been reported.In the present study, we investigated the effect of CYP lA l induction on oxidative status in the brain and liver.We demonstrated that induction of CYP lA l by 3-methylcholanthrene (3-MC) did not oxidize proteins or lipids, or decrease GS activity in rat brain and liver.Furthermore, the induction of CYP lA l in the brain and liver did not enhance the extent of lipid peroxidation in either tissue following oxidative challenge.If increased CYP lA l activity in the brain and liver following 3-MC treatment leads to increased ROS formation, the increase is insufficient to overwhelm the endogenous antioxidant defense system, produce detectable oxidative damage, and alter glutamate homeostasis.
Source: The Mathematics Enthusiast
Author: Liping Liu
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W2460985516