Science Inventory

Ozone-induced changes in oxidative stress parameters in brains of adult, middle-age, and senescent Brown Norway rats

Citation:

Kodavanti, P., J. Royland, J. Richards, D. Agina-Obu, AND R. Macphail. Ozone-induced changes in oxidative stress parameters in brains of adult, middle-age, and senescent Brown Norway rats. Presented at Society of Toxicology meeting, March 10 - 14, 2013.

Impact/Purpose:

This abstract will be presented at the Society of Toxicology meeting March 10-14, 2013, San Antonio, TX

Description:

Understanding life-stage susceptibility is a critical part of community based human health risk assessment following chemical exposure. Recently there is growing concern over a common air pollutant, ozone (03), and adverse health effects including dysfunction of the pulmonary, cardiac, and nervous systems. Oxidative stress (OS) is a known contributor in multiple organ toxicities and plays an important role in age-related diseases. Growing evidence implicates OS in 03 toxicity. The current study explored OS as a potential toxicity pathway for 03 exposure and addressed whether these effects are life stage-dependent. OS- related measures included reactive oxygen species (ROS) production [NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ)j, antioxidant homeostasis [total antioxidant substances (TA), superoxide dismutase (SOD), y-glutamylcysteine synthetase (‘y-GCS)j, and oxidative damage (total aconitase). Male Brown Norway rats (4, 12, and 24 months) were exposed to 03 (0, 0.25 or I ppm) via inhalation for 6 h/day, 2 days per week for 13 weeks. Frontal cortex (FC), cerebellum (CB), striatum (ST), and hippocampus (HP) were dissected 24 hours after last exposure, quick frozen, and stored at -80°C until analysis. Results indicated life stage-related increases in ROS production (—j 2x in UBIQ-RD and > 1.5x in NQOI in striatum), slight decreases in antioxidant homeostatic mechanisms (TAS, ‘y-GCS, and SOD), and a decrease in aconitase activity. The effects of 03 exposure were brain area-specific, with the striatum being more sensitive than other brain regions. With regard to life stage, the effects of 03 appeared to be greater in 4 month old than 12 or 24 month old rats. These results indicate OS could be a potential toxicity pathway for 03, but the complex interactions between age, exposure and brain region require further investigation. (This abstract does not necessarily reflect USEPA policy).

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 03/14/2013
Record Last Revised: 03/26/2013
OMB Category: Other
Record ID: 252239

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

TOXICOLOGY ASSESSMENT DIVISION

NEUROTOXICOLOGY BRANCH