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AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON PROTEIN CARBONYL CONTENT IN FRONTAL CORTEX AND CEREBELLUM OF BROWN NORWAY RATS.
KODAVANTI, PRASADA RAO S., J. E. ROYLAND, J. E. RICHARDS, J. BESAS, AND R. C. MACPHAIL. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON PROTEIN CARBONYL CONTENT IN FRONTAL CORTEX AND CEREBELLUM OF BROWN NORWAY RATS. . Presented at Annual Meeting of the Society of Toxicology, Baltimore, MD, March 15 - 19, 2009.
The influence of aging on susceptibility to environmental contaminants is poorly understood, largely due to a lack of data on exposures in older adults and adequate animal models. We examined the acute effects of the volatile organic compound, toluene, in a study investigating multiple toxicological endpoints. The objective of this study was to test whether oxidative stress plays a role in the adverse effects caused by toluene exposure, and if so, if effects were age-dependent. We selected protein carbonyl as an indicator of oxidative stress because carbonyl content of cells is a useful indicator of oxidative protein damage and has been linked to the adverse effects associated with chemical exposures. Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, brains were removed and placed on ice. Frontal cortex and cerebellum were dissected, quick frozen on dry ice, and stored at 80oC until analysis. Protein carbonyls were assayed using commercial kits. One-way ANOVA indicated that hydrogen peroxide, a positive control increased protein carbonyls in cortical tissue in vitro in a concentration-dependent manner. Two-way ANOVA indicated a significant effect of age and toluene on protein carbonyls in both frontal cortex and cerebellum. In control rats, there was an age-dependent increase in the protein carbonyls indicating increased oxidative stress in 24 month old rats compared to 4 or 12 month old rats. Although toluene increased protein carbonyls in both brain regions and in all age groups, step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate that frontal cortex and cerebellum of 12 month old rats are more susceptible to oxidative damage caused by toluene when compared to 4 month and 24 month old rats. (This abstract does not necessarily reflect USEPA policy).