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TOLUENE EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF YOUNG-ADULT, MIDDLE-AGE AND SENESCENT BROWN NORWAY RATS
KODAVANTI, PRASADA RAO S., J. E. ROYLAND, J. H. Richards, J. Besas, AND R. C. MACPHAIL. TOLUENE EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF YOUNG-ADULT, MIDDLE-AGE AND SENESCENT BROWN NORWAY RATS. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for toluene exposure (a hazardous air pollutant) and to determine if these effects were age-dependent.
Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for toluene exposure (a hazardous air pollutant) and to determine if these effects were age-dependent. We examined OS events to delineate reactive oxygen species production [NADPH Quinone oxidoreductase 1 (NQ01), NADH Ubiquinone reductase (UBIQ)], antioxidant homeostasis [total antioxidant substances (TAS) and superoxide dismutase (SOD)], and oxidative damage (total aconitase and protein carbonyls). Male Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Frontal cortex (FC), cerebellum (Cb), striatum (Str), and hippocampus (Hip) were dissected 4 hours after exposure, quick frozen, and stored at -80°C until analysis. Results indicated constitutive age-related changes in some OS parameters in selected brain regions (eg NQO 1 increase in Cb and TAS decrease in Str). Toluene effects on several OS endpoints were age-and brain region-specific. For example, toluene exposure increased NQ01 activity in FC and Cb at 4 and 12 months but only in Hip 9 and 24 months. In contrast, toluene decreased TAS levels at 4 months in all brain regions and at 24 months in Cb, but increased TAS levels at 12 and 24 months in FC, Cb, and Hip. Markers of oxidative damage reached significance only at selected ages and/or doses. Aconitase levels were increased at 12 months in FC at 0.65 and 1.0 g/kg, 24 months in FC at 0.65 g/kg, and 24 months in Cb at 1.0 g/kg toluene. Significant increases in protein carbonyl levels in both FC and Cb matched the pattern of aconitase in the FC. These results indicate OS as a potential toxicity pathway, but the complex interaction between age and toluene exposure on OS parameters in different brain regions requires further investigation. (This abstract does not necessarily reflect USEPA policy)