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首页> 美国政府科技报告 >Isolated Perfused Small Intestine-Application for Absorption and Metabolism of Trichloroethylene in the Fischer 344 Rat
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Isolated Perfused Small Intestine-Application for Absorption and Metabolism of Trichloroethylene in the Fischer 344 Rat

机译：分离灌注小肠 - 应用于Fischer 344大鼠中三氯乙烯的吸收和代谢

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Exposure by ingestion is the major route of exposure to toxic substances, particularly chemicals found in groundwater. Toxic substances which enter the body by this route may be metabolized to toxic intermediates which may then be exposed in high concentrations to the liver through the 'first pass effect', a physiological phenomenon occurring in the hepatic portal circulation. Because liver tumors in rodents are often the toxicity extrapolated to determine the 'human risk', the intestinal absorption and metabolism of orally- administered compounds should be extensively characterized. The objective of this study was to develop and validate the isolated vascularly perfused rat intestine model to examine the intestinal metabolism and rate of uptake of Air Force relevant compounds. The test compound used in this study was trichloroethylene (TRI), a chlorinated aliphatic hydrocarbon which has been linked to the formation of hepatic tumors in mice and renal tumors in rats. This study was successful in demonstrating the ability of this technique to successfully perfuse the vasculature of the rat small intestine. Microscopic examination of intestinal tissue post-perfusion showed no signs of tissue edema or cell damage compared to control non-perfused tissue. An average cumulative uptake of approximately 0.04% of the administered dose was observed. In addition, observance of metabolite formation revealed small amounts of TCOH was produced. The isolated vascularly perfused small intestine model can be a powerful investigative tool applicable to a variety of biomedical disciplines. In the future, data derived from our application of this system will be used to refine our understanding of gut metabolism and absorbence of chemicals and their metabolites - processes vital to toxicants whose exposure is primarily oral.

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