Hepatic Metabolism of Perfluorinated Carboxylic Acids andPolychlorotrifluoroethylene: A Nuclear Magnetic Resonance Investigation In vivo

摘要

This report describes recent results of studies designed to investigate themetabolic effects of perfluoro-carboxylic acids on liver carbohydrate and high-energy phosphorous metabolism. Carbon-13 nuclear magnetic resonance (NMR) spectroscopy was used in conjunction with (13) C isotope labeling to monitor the dynamic conversion of glucose to glycogen in rat liver in vivo. The results show that perfluoro-decanoic acid (PFDA) causes a marked inhibition in hepatic glycogen synthesis in rats at 3 days post treatment (n=5) and complete inhibition at 5 days post dose (n=5). Hepatic glucose and blood glucose levels are also slightly elevated within the first 15 min. following a glucose load in PFDA rats versus controls (p<0.05). Preliminary data reveal that glycogen synthesis from alanine via gluconeogenesis is functional in PFDA-treated rats. This suggests that the inhibition in glycogenesis from glucose may involve the transport of glucose into hepatocytes and/or its phosphorylation by glucokinase. Further studies are in progress which investigate this hypothesis. In studies of the high-energy phosphorous metabolism in PFDA-treated rats, (31)P NMR reveals normal ATP levels and an anomalous signal in the phosphomonoester region of the liver spectrum. The source of this phosphorous metabolite has not yet been identified and is the focus of ongoing research efforts. These studies are providing new information about the metabolic effects of perfluorocarboxylic acids and advancing the development of NMR techniques in the field of toxicology.