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同时暴露于 PCB126 和 PFOS 会增加与心血管疾病风险和肝损伤相关的生物标志物在小鼠体内的水平。

Co-exposure to PCB126 and PFOS increases biomarkers associated with cardiovascular disease risk and liver injury in mice.

机构信息

Superfund Research Center, University of Kentucky, Lexington, KY 40536, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.

Superfund Research Center, University of Kentucky, Lexington, KY 40536, USA.

出版信息

Toxicol Appl Pharmacol. 2020 Dec 15;409:115301. doi: 10.1016/j.taap.2020.115301. Epub 2020 Oct 20.

Abstract

Polychlorinated biphenyl (PCB)126 and perfluorooctane sulfonic acid (PFOS) are halogenated organic pollutants of high concern. Exposure to these chemicals is ubiquitous, and can lead to potential synergistic adverse effects in individuals exposed to both classes of chemicals. The present study was designed to identify interactions between PCB126 and PFOS that might promote acute changes in inflammatory pathways associated with cardiovascular disease and liver injury. Male C57BL/6 mice were exposed to vehicle, PCB126, PFOS, or a mixture of both pollutants. Plasma and liver samples were collected at 48 h after exposure. Changes in the expression of hepatic genes involved in oxidative stress, inflammation, and atherosclerosis were investigated. Plasma and liver samples was analyzed using untargeted lipidomic method. Hepatic mRNA levels for Nqo1, Icam1, and PAI1 were significantly increased in the mixture-exposed mice. Plasma levels of PAI1, a marker of fibrosis and thrombosis, were also significantly elevated in the mixture-exposed group. Liver injury was observed only in the mixture-exposed mice. Lipidomic analysis revealed that co-exposure to the mixture enhanced hepatic lipid accumulation and elevated oxidized phospholipids levels. In summary, this study shows that acute co-exposure to PCB126 and PFOS in mice results in liver injury and increased cardiovascular disease risk.

摘要

多氯联苯(PCB)126 和全氟辛烷磺酸(PFOS)是高度关注的卤代有机污染物。这些化学物质的暴露无处不在,并且可能导致同时接触这两类化学物质的个体产生潜在的协同不良反应。本研究旨在确定 PCB126 和 PFOS 之间的相互作用,这些相互作用可能会促进与心血管疾病和肝损伤相关的炎症途径的急性变化。雄性 C57BL/6 小鼠暴露于载体、PCB126、PFOS 或两者的混合物中。暴露后 48 小时采集血浆和肝脏样本。研究了参与氧化应激、炎症和动脉粥样硬化的肝脏基因的表达变化。使用非靶向脂质组学方法分析血浆和肝脏样本。混合物暴露组小鼠肝脏中 Nqo1、Icam1 和 PAI1 的 mRNA 水平显著升高。混合物暴露组血浆中 PAI1(纤维化和血栓形成的标志物)水平也显著升高。仅在混合物暴露组小鼠中观察到肝损伤。脂质组学分析表明,混合物的共同暴露增强了肝脏脂质积累并升高了氧化磷脂水平。总之,这项研究表明,急性共暴露于 PCB126 和 PFOS 会导致小鼠肝损伤和增加心血管疾病风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71a7/7725976/6b61e3c65bf3/nihms-1639310-f0001.jpg

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