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BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS.
KODAVANTI, PRASADA RAO S., J. E. RICHARDS, M. SCHLADWEILER, U. P. KODAVANTI, J. D. FARMER, AND R. C. MACPHAIL. BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS. Presented at American Society for Neurochemistry, Portland, OR, March 11 - 15, 2006.
Animal models of susceptibility are critical for human health risk assessment. Previous studies indicate that spontaneously hypertensive (SHR) rats are more sensitive than Wistar-Kyoto (WKY) rats to the cholinesterase (ChE) inhibitors such as carbaryl and chlorpyrifos. This differential sensitivity was not explained by the ChE inhibition. Since SHRs are oxidative stress (OS) prone rats, one hypothesis is that SHRs are more sensitive to chemical-induced oxidative injury compared to WKYs. Our initial experiments focused on measuring aconitase activity as an OS indictor in SHR and WKY rats with out any chemical exposure, since brain OS parameters in SHRs were not fully characterized. The brain regions (frontal cortex, parietal cortex, cerebellum, hippocampus, hypothalamus, and striatum) as well as other organs such as heart, lung, liver, kidney, and testis were isolated from twelve SHRs and twelve WKYs, quick frozen on dry ice, and stored at -80oC. The tissues were homogenized in 20 mM Tris buffer (pH 7.4) and centrifuged at 8000 g for 20 min. The supernatants were assayed for total aconitase activity using the kit from Oxis International Inc. Among the organs, aconitase activity was greater in the kidney. Among the brain regions, the hippocampus has greater aconitase activity. Total aconitase activity in all organs was significantly lower in SHR compared to WKY. These results suggest that oxidative burden is greater in all organs in SHR compared to WKY, and that SHR's can be used in toxicity testing to understand the role of OS in the adverse effects associated with chemical exposures. (This abstract does not necessarily reflect USEPA policy).
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
CELLULAR AND MOLECULAR TOXICOLOGY BRANCH