Gordon Christopher J, Ward William O
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, MD B105-04, 109 TW Alexander Drive, Research Triangle Park, NC 27711, United States.
Neurotoxicology. 2009 May;30(3):377-81. doi: 10.1016/j.neuro.2009.02.009. Epub 2009 Feb 24.
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 with 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 24h 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 (four up, two down) following CHP and eight analytes (five up, three down) following CAR at 24h. 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.
高通量生化筛选技术的发展可能有助于评估环境毒物的广泛生理效应。为了探索在体内暴露情况下使用该筛选技术的前景,我们将一种包含58种血清生物标志物的市售多分析物谱(MAP)应用于急性暴露于两种抗胆碱酯酶杀虫剂毒死蜱(CHP)和西维因(CAR)的大鼠。雄性Long-Evans大鼠经口给予30 mg/kg CHP、75 mg/kg CAR或玉米油载体。根据它们等效的生理效应(体温过低和运动活动减少)选择剂量。给药后24小时或7天处死动物。收集血清并分析58种主要由细胞因子、趋化因子和一些激素组成的生物标志物。CHP给药后24小时有6种分析物发生变化(4种升高,2种降低),CAR给药后有8种分析物发生变化(5种升高,3种降低)。CHP给药7天后仅两种生物标志物有显著变化。总体而言,MAP检测到CHP和CAR具有广泛的独特效应。结论是,MAP是筛选环境毒物体内效应的有用工具,其应用可能会发现新的作用机制。