Wan H T, Zhao Y G, Wei X, Hui K Y, Giesy J P, Wong Chris K C
Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, 200 Waterloo Road, Kowloon Tong, Hong Kong, China.
Biochim Biophys Acta. 2012 Jul;1820(7):1092-101. doi: 10.1016/j.bbagen.2012.03.010. Epub 2012 Mar 28.
Perfluorooctane sulfonate (PFOS) was produced by various industries and was widely used in diverse consumer products. Human sample analysis indicated PFOS contamination in body fluids. Animal studies revealed that PFOS tends to accumulate in livers and is able to induce hepatomegaly. However the underlying mechanism of PFOS-elicited hepatotoxicity has not yet been fully addressed. The objective of this study is to identify the cellular target of PFOS and to reveal the mechanisms of PFOS-induced toxicity.
In this study, mature 8-week old male CD-1 mice were administered 0, 1, 5 or 10 mg/kg/day PFOS for 3, 7, 14 or 21 days. Histological analysis of liver sections, and biochemical/molecular analysis of biomarkers for hepatic lipid metabolism were assessed.
PFOS-induced steatosis was observed in a time- and dose-dependent manner. The gene expression levels of fatty acid translocase (FAT/CD36) and lipoprotein lipase (Lpl) were significantly increased by 10 and/or 5 mg/kg PFOS. Serum levels of very-low density lipoprotein were decreased by 14 days of PFOS exposure (p<0.05). The rate of mitochondrial β-oxidation was also found to be significantly reduced, leading to the restriction of fatty acid oxidation for energy production.
Taken together, the disturbance of lipid metabolism leads to the accumulation of excessive fatty acids and triglycerides in hepatocytes.
Since PFOS-elicited pathological manifestation resembles one of the most common human liver diseases-nonalcoholic fatty liver disease, environmental exposure to PFOS may attribute to the disease progression.
全氟辛烷磺酸（PFOS）由多个行业生产，并广泛应用于各种消费品中。人体样本分析表明体液中存在PFOS污染。动物研究显示，PFOS易于在肝脏中蓄积，并能够诱发肝肿大。然而，PFOS引发肝毒性的潜在机制尚未完全阐明。本研究的目的是确定PFOS的细胞靶点，并揭示PFOS诱导毒性的机制。
在本研究中，8周龄成熟雄性CD-1小鼠分别给予0、1、5或10mg/kg/天的PFOS，持续3、7、14或21天。对肝脏切片进行组织学分析，并对肝脏脂质代谢的生物标志物进行生化/分子分析。
观察到PFOS诱导的脂肪变性呈时间和剂量依赖性。10mg/kg和/或5mg/kg的PFOS可显著提高脂肪酸转运蛋白（FAT/CD36）和脂蛋白脂肪酶（Lpl）的基因表达水平。PFOS暴露14天后，极低密度脂蛋白的血清水平降低（p<0.05）。还发现线粒体β-氧化速率显著降低，导致脂肪酸氧化受限，无法产生能量。
综上所述，脂质代谢紊乱导致肝细胞中过量脂肪酸和甘油三酯的蓄积。
由于PFOS引发的病理表现类似于人类最常见的肝脏疾病之一——非酒精性脂肪性肝病，环境暴露于PFOS可能与该疾病的进展有关。
