Massey Veronica L, Stocke Kendall S, Schmidt Robin H, Tan Min, Ajami Nadim, Neal Rachel E, Petrosino Joseph F, Barve Shirish, Arteel Gavin E
Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292, USA.
Department of Environmental and Occupational Health Sciences, School of Public Health, University of Louisville Health Sciences Center, Louisville, KY 40292, USA.
Toxicol Appl Pharmacol. 2015 May 1;284(3):304-14. doi: 10.1016/j.taap.2015.02.022. Epub 2015 Mar 8.
Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is known to cause liver injury. Although the concentrations of As found in the US water supply are generally too low to directly damage the liver, subhepatotoxic doses of As sensitize the liver to experimental NAFLD. It is now suspected that GI microbiome dysbiosis plays an important role in development of NALFD. Importantly, arsenic has also been shown to alter the microbiome. The purpose of the current study was to test the hypothesis that the prebiotic oligofructose (OFC) protects against enhanced liver injury caused by As in experimental NAFLD. Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD containing oligofructose (OFC) during concomitant exposure to either tap water or As-containing water (4.9ppm as sodium arsenite) for 10weeks. HFD significantly increased body mass and caused fatty liver injury, as characterized by an increased liver weight-to-body weight ratio, histologic changes and transaminases. As observed previously, As enhanced HFD-induced liver damage, which was characterized by enhanced inflammation. OFC supplementation protected against the enhanced liver damage caused by As in the presence of HFD. Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora. These data support previous findings that low concentrations of As enhance liver damage caused by high fat diet. Furthermore, these results indicate that these effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and that prebiotic supplementation may confer significant protective effects.
砷（As）在有毒环境化学物质的美国毒物与疾病登记署（ATSDR）名单上位居榜首，并且已知会导致肝损伤。尽管在美国供水系统中发现的砷浓度通常过低，无法直接损害肝脏，但亚肝毒性剂量的砷会使肝脏对实验性非酒精性脂肪性肝病（NAFLD）敏感。现在怀疑胃肠道微生物群失调在NAFLD的发展中起重要作用。重要的是，砷也已被证明会改变微生物群。本研究的目的是检验以下假设：益生元低聚果糖（OFC）可预防实验性NAFLD中由砷引起的肝损伤加重。雄性C57Bl6/J小鼠在同时暴露于自来水或含砷水（4.9ppm亚砷酸钠）10周期间，分别喂食低脂饮食（LFD）、高脂饮食（HFD）或含低聚果糖（OFC）的HFD。HFD显著增加体重并导致脂肪肝损伤，其特征为肝重与体重比增加、组织学变化和转氨酶升高。如先前观察到的，砷加重了HFD诱导的肝损伤，其特征为炎症增强。补充OFC可预防在HFD存在的情况下由砷引起的肝损伤加重。有趣的是，砷、HFD和OFC均对肠道菌群造成了独特的改变。这些数据支持了先前的研究结果，即低浓度的砷会加重高脂饮食引起的肝损伤。此外，这些结果表明，砷的这些作用可能至少部分是由胃肠道失调介导的，并且补充益生元可能具有显著的保护作用。
