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A multi-analyte profile of serum proteins to screen for toxicological effects of anticholinesterase insecticides in the rat
Citation:
GORDON, C. J. AND W. O. WARD. A multi-analyte profile of serum proteins to screen for toxicological effects of anticholinesterase insecticides in the rat. Presented at Annual Meeting of the Society of Toxicology, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
This paper provides a novel approach to characterize in vivo toxicological response using a panel of 58 serum biomarkers. Using two anticholinesterase insecticides as test agents, unique patterns of activation and suppression of select serum biomarkers were observed. The patterns of activation may be utilized to understand the mechanism of action of single agents and mixtures of insecticides and other environmental toxicants.
Description:
The development of high throughput biochemical screens could be useful to assess the broad spectrum of physiological effects of environmental toxicants. To explore the prospect of using a screen in an in vivo exposure scenario, we applied a commercially available multianalyte profile (MAP) of 58 serum biomarkers to rats exposed acutely to two anticholinesterase insecticides, chlorpyrifos (CHP) and carbaryl (CAR). Male, Long-Evans rats were dosed orally to 30 mg/kg CHP, 75 mg/kg CAR or the corn oil vehicle. Doses were selected based on their equivalent physiological effects (hypothermia and reduced motor activity). The animals were terminated 24 hours or 7 days after dosing. Serum was collected and analyzed for 58 biomarkers consisting primarily of cytokines, chemokines, and a few hormones. There were changes in six analytes (4 up, 2 down) following CHP and eight analytes (5 up, 3 down) following CAR at 24 hours. There were significant changes in only two biomarkers when measured 7 days after dosing with CHP. Overall, the MAP detected a broad spectrum of unique effects for CHP and CAR. It is concluded that the MAP is a useful tool to screen for in vivo effects of environmental toxicants and its use could lead to the discovery of novel mechanisms of action.