Hepatic Metabolism of Perfluorinated Carboxylic Acids andPolychlorotrifluoroethylene: A Nuclear Magnetic Resonance Investigation in vitro

摘要

During the past year, this research program has focus in two main areas relatingto the effects of PFOA and PFDA on hepatic metabolism, namely phospholipid and carbohydrate metabolism. Through the use of NMR spectroscopy and standard biochemical assays, these studies have probed specific metabolic pathways and examined the impact of perfluorocarboxylic acid exposure. This investigative strategy will delineate the metabolic effices exerted by these compounds and aid in developing a clearer understanding of the hepatotoxic mechanisms at play. In summary, these studies have demonstrated that PFDA treatment exhibits unique metabolic effects which are not observed with PFOA. PFDA depresses glucose transport into hepatocytes and inhibits glycogen synthesis. It also shows dramatic effects upon hepatic phospholipid metabolism. PFDA activates a phosphatidylcholine-specific phospholipase C which has important implications with regard to various cellular processes. It is likely that this effect of PFDA may trigger a cellular signaling mechanism through diacyglycerol and subsequent activation of protein kinase C. Current investigation in our laboratory are addressing these cellular metabolites, enzymes, and pathways. These research endeavors will provide new information regarding the mechanisms of toxicity associated with a class of compounds which are important in various Air Force applications.