Influence of carbon chain length on the hepatic effects of perfluorinated fatty acids. A F-19- and P-31-NMR investigation
Influence of carbon chain length on the hepatic effects of perfluorinated fatty acids. A F-19- and P-31-NMR investigation
复制标题
DOI：
10.1021/tx950217k
复制
发表时间：
1996-06-01
影响因子：
4.1
通讯作者：
Reo, NV
中科院分区：
文献类型：
--
作者：
GoeckeFlora, CM;Reo, NV
利用核磁共振波谱，我们研究了碳链长度对于全氟正羧酸对肝脏的影响的重要性。给雄性F-344大鼠单次腹腔注射全氟正庚酸(C-7-PFA)、全氟正十一酸(C-9-PFA)或全氟正十一酸(C-11-PFA)。本文还包括了以前涉及全氟正辛酸(C8-PFA)和全氟正庚酸(C-10-PFA)的研究数据，以供比较。每天监测所有组的食物消耗量/体重。C-9-PFA和C-11-PFA的低吞噬反应持续时间延长，而C-7-PFA则表现出更剧烈的反应。尿液和胆汁样品的~(19)F核磁共振谱未显示出新的代谢产物，表明全氟碳化合物在尿液或胆汁中的分布与碳链长度有关。C-7-PFA的水溶性似乎促进了尿液的快速排泄，与C-8-PFA的观察结果相似。C-9-和C-11-PFA的相对疏水性似乎有利于胆肠-肝循环，产生与C-10-PFA相似的更持久的毒性。活体肝脏和肝脏提取物的31P核磁共振研究表明，大于或等于C-9碳的全氟碳会显著增加肝脏磷胆碱的浓度。这些数据讨论了这些化学物质对肝脏磷脂代谢的影响。测定肝脏过氧化物体脂肪酰辅酶A氧化酶活性(FAO)，以确定C-7、C-9和C-11-PFA是否为过氧酶体增殖物。数据表明，全氟化碳诱导过氧化物酶活性需要超过7个碳的链长。总的来说，这些结果证明了碳链长度在肝毒性反应中的重要性，并为理解与接触这些化合物相关的生物学活动所涉及的过程提供了线索。
Using nuclear magnetic resonance (NMR) spectroscopy, we investigated the importance of carbon chain length with regard to the hepatic effects associated with perfluoro-n-carboxylic acids. Male F-344 rats were administered a single intraperitoneal dose of either perfluoro-n-heptanoic acid (C-7-PFA), perfluoro-n-nonanoic acid (C-9-PFA), or perfluoro-n-undecanoic acid (C-11-PFA). Data from previous studies involving perfluoro-n-octanoic acid (C8-PFA) and perfluoro-n-decanoic acid (C-10-PFA) are included for comparison. Food consumption/body weight was monitored daily for all groups. C-9- and C-11-PFA treatment yields a prolonged hypophagic response while C-7-PFA shows a more acute response. Fluorine-19 NMR spectra of urine and bile samples show no evidence of nuorometabolites and suggest that the distribution of perfluorocarbons into urine or bile is dependent upon carbon chain length. The aqueous solubility of C-7-PFA appears to facilitate rapid urinary excretion, similar to that observed for C-8-PFA. The relative hydrophobicity of C-9- and C-11-PFA appears to favor biliary enterohepatic recirculation, yielding a more protracted toxicity, similar to C-10-PFA. Phosphorus-31 NMR studies of liver in vivo and liver extracts show that perfluorocarbons of greater than or equal to C-9 carbons produce a significant increase in liver phosphocholine concentration. These data are discussed with regard to the impact of these chemicals on hepatic phospholipid metabolism. Hepatic peroxisomal fatty acyl CoA-oxidase activity (FAO) was measured to determine if C-7-, C-9-, and C-11-PFA are peroxisome proliferators. Data indicate that the induction of peroxisomal enzyme activity by perfluorocarbons requires a chain length greater than seven carbons. In general, these results demonstrate the significance of carbon chain length in the hepatotoxic response and provide clues toward understanding the processes involved in the biological activities associated with exposure to these compounds.