Hepatic Metabolism of Perfluorinated Carboxylic Acids and Polychlorotrifluoroethylene: A Nuclear Magnetic Resonance Investigation in Vivo.

摘要

This report outlines our research progress regarding toxicological investigations of perfluoron-octanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA). These compounds and related fluorocarbon compounds are useful in Air Force applications as solvents, lubricants, and surfactants. Unfortunately, many of these compounds display hepatotoxic effects. Recent studies in our laboratory have shown that PFDA displays unique effects upon liver metabolism which are not observed with PFOA treatment. Specific effects on phospholipid metabolism Include an induction in phosphatidylcholine-specific phospholipase C activity and inhibition in CTP:phosphocholine cytidylyltransferase activity. These enzymes regulate phosphatidylcholine degradation and biosynthesis, respectively. These data suggest that diacylglycerol may be elevated which can affect various cellular processes through a second-messenger signaling mechanism. Other studies in the laboratory have shown that PFDA inhibits hepatic glycogen synthesis by decreasing glucose transport activity. PFDA-treated rats show rates of glucose transport which are 1.8-fold less than that for corresponding controls (p = 0.02). PFDA-treatment also impacts the relative activity of pyruvate carboxylase and pyruvate dehydrogenase-enzymes involved in the regulation of both carbohydrate and lipid metabolism. These research activities further our understanding of the mechanisms involved in the hepatotoxicity associated with these important Air Force chemicals. Toxicology.