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

Abstract

A critical part of community based human health risk assessment following chemical exposure is identifying sources of susceptibility. Life stage is one such susceptibility. A prototypic air pollutant, ozone (O3) induces dysfunction of the pulmonary, cardiac, and nervous systems. Long-term exposure may cause oxidative stress (OS). The current study explored age-related and subchronic O3-induced changes in OS in brain regions of rats. To build a comprehensive assessment of OS-related effects of O3, a tripartite approach was implemented focusing on 1) the production of reactive oxygen species (ROS) [NADPH Quinone oxidoreductase 1, NADH Ubiquinone reductase] 2) antioxidant homeostasis [total antioxidant substances, superoxide dismutase, γ-glutamylcysteine synthetase] and 3) an assessment of oxidative damage [total aconitase and protein carbonyls]. Additionally, a neurobehavioral evaluation of motor activity was compared to these OS measures. Male Brown Norway rats (4, 12, and 24 months of age) were exposed to air or O3 (0.25 or 1 ppm) via inhalation for 6 h/day, 2 days per week for 13 weeks. A significant decrease in horizontal motor activity was noted only in 4-month old rats. Results on OS measures in frontal cortex (FC), cerebellum (CB), striatum (STR), and hippocampus (HIP) indicated life stage-related increases in ROS production, small decreases in antioxidant homeostatic mechanisms, a decrease in aconitase activity, and an increase in protein carbonyls. The effects of O3 exposure were brain area-specific, with the STR being more sensitive. Regarding life stage, the effects of O3 were greater in 4-month-old rats, which correlated with horizontal motor activity. These results indicate that OS may be increased in specific brain regions after subchronic O3 exposure, but the interactions between age and exposure along with their consequences on the brain require further investigation.