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蛋白质组学评价恩镰菌素急性毒性对大鼠肝脏的影响。

Proteomics evaluation of enniatins acute toxicity in rat liver.

机构信息

Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, Universitat de València, Carrer Vicent Andrés Estellés s/n, 46100, Bujassot, Spain.

Laboratory of Food Chemistry and Toxicology, Faculty of Pharmacy, Universitat de València, Carrer Vicent Andrés Estellés s/n, 46100, Bujassot, Spain.

出版信息

Food Chem Toxicol. 2021 May;151:112130. doi: 10.1016/j.fct.2021.112130. Epub 2021 Mar 16.

DOI:10.1016/j.fct.2021.112130
PMID:33741480
Abstract

Enniatins (ENs) are emerging mycotoxins produced by Fusarium fungi which are cytotoxic also at low concentrations due to its ionophoric properties. The aim of this study was to evaluate the hepatic toxicity of ENs exposure at different concentrations in Wistar rats through a proteomic approach. Animals were intoxicated by oral gavage with medium (EN A 256, ENA1 353, ENB 540, ENB1 296 μg/mL) and high concentrations (ENA 513, ENA1 706, ENB 1021, ENB1 593 μg/mL) of an ENs mixture and sacrificed after 8 h. Protein extraction was performed using powdered liver. Peptides were analyzed using a liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Proteins were filtered by abundance using Mass Professional Profiler software (Agilent Technologies) and 57 were differentially expressed when compared to the control. In terms of abundance, the liver biomarker Carboamoyl-phosphate synthase showed the highest levels in all conditions employed while actin-1 had the lowest. Bioinformatic analysis using DAVID platform reported acetylation, nucleotide phosphate-binding region:NAD and catalytic activity as the most represented terms. Furthermore, metabolism was the most significant and enriched pathway in Reactome overrepresentation. In conclusion, ENs acute exposure caused protein expression changes related to major cellular processes in rats, hinting its involvement in liver disturbance.

摘要

恩镰菌素(ENs)是由镰刀菌产生的新兴霉菌毒素,由于其具有离子载体特性,即使在低浓度下也具有细胞毒性。本研究旨在通过蛋白质组学方法评估不同浓度 ENs 暴露对 Wistar 大鼠肝脏的毒性。动物通过口服灌胃方式摄入中浓度(EN A 256、ENA1 353、ENB 540、ENB1 296μg/mL)和高浓度(ENA 513、ENA1 706、ENB 1021、ENB1 593μg/mL)的 ENs 混合物,并在 8 小时后处死。使用粉末状肝脏进行蛋白质提取。使用液相色谱-四极杆飞行时间质谱联用仪分析肽。使用 Mass Professional Profiler 软件(Agilent Technologies)根据丰度过滤蛋白质,与对照组相比,有 57 种蛋白质表达差异。就丰度而言,在所有实验条件下,Carboamoyl-phosphate synthase 是肝脏生物标志物中含量最高的,而肌动蛋白-1 则含量最低。使用 DAVID 平台进行的生物信息学分析报告了乙酰化、核苷酸磷酸结合区:NAD 和催化活性是最具代表性的术语。此外,在 Reactome 中的过表达分析中,代谢是最重要和最富集的途径。总之,ENs 急性暴露导致大鼠细胞内主要过程的蛋白质表达发生变化,提示其参与肝脏紊乱。

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