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采用蛋白质组学分析评估 3-MCPD 1-单油酸酯和 1-单硬脂酸酯暴露雄性 Sprague Dawley 大鼠 90 天的肾毒性。

Ninety-Day Nephrotoxicity Evaluation of 3-MCPD 1-Monooleate and 1-Monostearate Exposures in Male Sprague Dawley Rats Using Proteomic Analysis.

机构信息

Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.

Diet, Genomics, and Immunology Laboratory, Agricultural Research Service (ARS), USDA, Beltsville, Maryland 20705, United States.

出版信息

J Agric Food Chem. 2020 Mar 4;68(9):2765-2772. doi: 10.1021/acs.jafc.0c00281. Epub 2020 Feb 21.

Abstract

Fatty acid esters of 3-monochloropropane 1,2-diol (3-MCPD esters) are processing-induced food toxicants, with the kidney as their major target organ. For the first time, this study treated Sprague Dawley (SD) rats with 3-MCPD 1-monooleate at 10 and 100 mg/kg BW/day and 1-monostearate at 15 and 150 mg/kg BW/day for 90 days and examined for their potential semi-long-term nephrotoxicity and the associated molecular mechanisms. No bodyweight difference was observed between groups during the study. Both 3-MCPD 1-monooleate and 1-monostearate resulted in a dose-dependent increase of serum urea creatinine, uric acid and urea nitrogen levels, and histological renal impairment. The proteomic analysis of the kidney samples showed that the 3-MCPD esters deregulated proteins involved in the pathways for ion transportation, apoptosis, the metabolism of xenobiotics, and enzymes related to endogenous biological metabolisms of carbohydrates, amino acids, nitrogen, lipids, fatty acids, and the tricarboxylic acid (TCA) cycle, providing partial explanation for the nephrotoxicity of 3-MCPD esters.

摘要

3-单氯丙二醇脂肪酸酯(3-MCPD 酯)是加工过程中产生的食品毒物,其主要靶器官是肾脏。本研究首次以 10 和 100mg/kg BW/天的剂量和 15 和 150mg/kg BW/天的剂量分别用 3-MCPD 1-单油酸酯和 1-单硬脂酸酯处理 Sprague Dawley(SD)大鼠 90 天,研究其潜在的半长期肾毒性及其相关分子机制。研究过程中各组间体重无差异。3-MCPD 1-单油酸酯和 1-单硬脂酸酯均导致血清尿素、肌酐、尿酸和尿素氮水平呈剂量依赖性升高,并伴有组织学肾损伤。肾脏样本的蛋白质组学分析表明,3-MCPD 酯调节了与离子转运、细胞凋亡、外源生物代谢途径以及与碳水化合物、氨基酸、氮、脂质、脂肪酸和三羧酸(TCA)循环内源性生物代谢相关的酶相关的蛋白。这为 3-MCPD 酯的肾毒性提供了部分解释。

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