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解析丙烯酰胺诱导的心血管毒性的血清代谢组学特征。

Unraveling the Serum Metabolomic Profile of Acrylamide-Induced Cardiovascular Toxicity.

机构信息

National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, College of Biosystems Engineering and Food Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, China.

Department of Nutrition and Food Hygiene, School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.

出版信息

J Agric Food Chem. 2021 Oct 13;69(40):12012-12020. doi: 10.1021/acs.jafc.1c04367. Epub 2021 Sep 29.

DOI:10.1021/acs.jafc.1c04367
PMID:34586797
Abstract

Acrylamide has been reported as an important dietary risk factor from carbohydrate-rich processing food. However, systemic biological effects on the serum metabolomics induced by acrylamide have poorly been understood. In the present study, we evaluated the metabolic profiles in a rat serum after exposure to acrylamide using ultrahigh-performance liquid chromatography combined with quadrupole-orbitrap high-resolution mass spectrometry. The serum biochemical parameters of the treated and control groups were also determined using an automatic biochemical analyzer. Compared with the control group, 10 metabolites were significantly upregulated, including citric acid, d-(-)-fructose, gluconic acid, l-ascorbic acid 2-sulfate, 2-hydroxycinnamic acid, valine, l-phenylalanine, prolylleucine, succinic acid, and cholic acid, while 5 metabolites were significantly downregulated, including 3-hydroxybutyric acid, 4-oxoproline, 2,6-xylidine, 4-phenyl-3-buten-2-one, and -ethyl--methylcathinone in the serum of 4-week-old rats exposed to acrylamide in the high-dose group (all < 0.05). Importantly, acrylamide exposure affected metabolites mainly involved in the citrate cycle, valine, leucine, and isoleucine biosyntheses, phenylalanine, tyrosine and tryptophan biosyntheses, and pyruvate metabolism. These results suggested that exposure to acrylamide in rats exhibited marked systemic metabolic changes and affected the cardiovascular system. This study will provide a theoretical basis for exploring the toxic mechanism and will contribute to the diagnosis and prevention of acrylamide-induced cardiovascular toxicity.

摘要

丙烯酰胺已被报道为富含碳水化合物的加工食品中的重要饮食风险因素。然而,其对血清代谢组学的系统生物学影响仍知之甚少。在本研究中,我们使用超高效液相色谱-四极杆轨道阱高分辨质谱联用技术评估了丙烯酰胺暴露后大鼠血清中的代谢谱。还使用自动生化分析仪测定了处理组和对照组的血清生化参数。与对照组相比,10 种代谢物在丙烯酰胺高剂量组的 4 周龄大鼠血清中显著上调,包括柠檬酸、d-(-)-果糖、葡萄糖酸、l-抗坏血酸 2-硫酸盐、2-羟基肉桂酸、缬氨酸、l-苯丙氨酸、脯氨酰亮氨酸、琥珀酸和胆酸,而 5 种代谢物显著下调,包括 3-羟基丁酸、4-氧脯氨酸、2,6-二甲氧基吡啶、4-苯基-3-丁烯-2-酮和 -乙基--甲基卡他碱(所有 P 值均 < 0.05)。重要的是,丙烯酰胺暴露主要影响参与柠檬酸循环、缬氨酸、亮氨酸和异亮氨酸生物合成、苯丙氨酸、酪氨酸和色氨酸生物合成以及丙酮酸代谢的代谢物。这些结果表明,丙烯酰胺暴露在大鼠中表现出明显的系统性代谢变化,并影响心血管系统。本研究将为探索其毒性机制提供理论依据,并有助于丙烯酰胺诱导的心血管毒性的诊断和预防。

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