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大鼠血清中长期低水平接触丙烯酰胺的毒作用代谢组学分析。

Metabonomic analysis of toxic action of long-term low-level exposure to acrylamide in rat serum.

机构信息

Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China.

College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Hum Exp Toxicol. 2018 Dec;37(12):1282-1292. doi: 10.1177/0960327118769708. Epub 2018 Apr 16.

DOI:10.1177/0960327118769708
PMID:29658313
Abstract

This study assessed the effects of long-term, low-dose acrylamide (AA) administration in rats using ultra-performance liquid chromatography-mass spectrometry. Forty male Wistar rats were randomly divided into the following four groups: control, low-dose AA (0.2 mg/kg BW), middle-dose AA (1 mg/kg BW), and high-dose AA (5 mg/kg BW). AA was administered to rats via drinking water ad libitum. After 16-week treatment, rat serum was collected for metabonomic analysis. Biochemical tests were further conducted to verify metabolic alterations. Eleven metabolites were identified with significant changes in intensities (increased or reduced) as a result of treatment. These metabolites included citric acid, pantothenic acid, isobutyryl-l-carnitine, eicosapentaenoic acid, docosahexaenoic acid, sphingosine 1-phosphate, LysoPC(20:4), LysoPC(22:6), LysoPE(20:3), undecanedioic acid, and dodecanedioic acid. Results indicate that chronic exposure to AA at no observed adverse effect level does not exert a toxic effect on rats at the body metabolism level. AA disturbed the metabolism of lipids and energy, affected the nervous system of rats, and induced oxidative stress and liver dysfunction.

摘要

本研究采用超高效液相色谱-质谱联用技术评估了长期低剂量丙烯酰胺(AA)在大鼠体内的作用。将 40 只雄性 Wistar 大鼠随机分为以下四组:对照组、低剂量 AA(0.2mg/kgBW)组、中剂量 AA(1mg/kgBW)组和高剂量 AA(5mg/kgBW)组。AA 通过自由饮水的方式给予大鼠。经过 16 周的治疗后,收集大鼠血清进行代谢组学分析。进一步进行生化测试以验证代谢变化。由于处理,11 种代谢物的强度(增加或减少)发生了显著变化。这些代谢物包括柠檬酸、泛酸、异丁酰肉碱、二十碳五烯酸、二十二碳六烯酸、鞘氨醇 1-磷酸、LysoPC(20:4)、LysoPC(22:6)、LysoPE(20:3)、十一烷二酸和十二烷二酸。结果表明,在无观察到不良作用水平下,慢性接触 AA 不会在大鼠的全身代谢水平上产生毒性作用。AA 扰乱了脂质和能量代谢,影响了大鼠的神经系统,并诱导了氧化应激和肝功能障碍。

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