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DIFFERENTIAL EFFECTS OF CARBARYL IN BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS.
Citation:
KODAVANTI, PRASADA RAO S., T. R. WARD, J. E. RICHARDS, M. SCHLADWEILER, U. P. KODAVANTI, J. D. FARMER, AND R. C. MACPHAIL. DIFFERENTIAL EFFECTS OF CARBARYL IN BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Animal models of susceptibility are crucial for quantitative human health risk assessment. Spontaneously hypertensive rats (SHR) have long been used in studies on the etiology and mechanisms of hypertension and are known to be prone to oxidative stress. Previous studies indicate that SHRs are more sensitive to the cholinesterase (ChE) inhibitor carbaryl than Wistar-Kyoto rats (WKY), and this could not be explained by ChE inhibition. We have recently confirmed the differential sensitivity of SHRs to carbaryl on motor activity. One hypothesis is that SHRs are more sensitive to carbaryl-induced oxidative injury compared to WKYs. Therefore, we compared levels of aconitase, a key enzyme in oxidative stress, in frontal cortex and cerebellum of adult SHRs and WKYs. Groups of ten SHRs and ten WKYs were administered carbaryl (0, 5, or 50 mg/kg in corn oil) by oral gavage. At 1 hour post-dosing, the brain regions (frontal cortex and cerebellum) were isolated, quick frozen on dry ice, and stored at -80oC. The brain regions 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. It is known that aconitase in cytosol maintains iron homeostasis; mitochondrial aconitase on the other hand is used as a marker of oxidative stress. Total aconitase activity in frontal cortex was not affected by carbaryl treatment either in SHRs or WKYs. On the other hand, total aconitase activity in cerebellum was significantly inhibited by carbaryl in SHR rats, but not in WKY rats. These results suggest that carbaryl causes oxidative stress in the cerebellum at a subcellular level in oxidative stress prone SHRs and provide further support for a novel mechanism underlying carbaryl effects on motor activity. (This abstract does not necessarily reflect USEPA policy).