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AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS.
Citation:
ROYLAND, J. E., J. E. RICHARDS, J. Besas, AND R. C. MACPHAIL. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS. Presented at Society of Toxicology 49th annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent.
Description:
The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We selected oxidative stress parameters to delineate the production of reactive oxygen species [NADPH Quinone oxidoreductase 1 (NQOl), NADH Ubiquinone reductase (UBIQ)]' antioxidant homeostasis [total antioxidant substances (TAS) and glutathione metabolism (SOD, GCS, GST, GPX and GRD)], and oxidative damage (total aconitase and protein carbonyls). Male Brown Norway rats (4, 12, and 24 mos) were dosed orally with toluene (0, 0.65 or 1 g/kg) in com oil. Four hours later, frontal cortex (FC), cerebellum (Cb), striatum (Str), and hippocampus (Hip) were dissected out, quick frozen, and stored at -80°C until analysis. Results indicated constitutive age-related changes in some parameters in selected brain regions (eg NQ01 in Cb and TAS in Str). Toluene effects on several OS endpoints were age-and brain region-specific. For example, toluene exposure increased NQO 1 activity at 4 and 12 mos in FC and Cb but only at 24 mos in Hip. In contrast, toluene decreased TAS levels at 4 mos in all brain regions and at 24 mos in Cb, but increased TAS levels at 12 and 24 mos in FC, Cb, and Hip. Toluene effects on glutathione enzymes were also age-and brain region-specific. Markers of oxidative damage reached significance only at selected ages and/or doses. Aconitase levels were increased in 12 mos FC at 0.65 and 1.0 g/kg, 24 mos in FC at 0.65 g/kg, and 24 mos 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 brain needs further evaluation. (This abstract does not necessarily reflect USEPA policy).