Metabolomics strategy comprehensively unveils the effect of catechins intervention on the biomarkers of exposure to acrylamide and biomarkers of cardiometabolic risk.
Metabolomics strategy comprehensively unveils the effect of catechins intervention on the biomarkers of exposure to acrylamide and biomarkers of cardiometabolic risk.
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DOI：
10.1016/j.envint.2022.107517
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发表时间：
2022-09
影响因子：
11.8
通讯作者：
Xuzhi Wan;Wei Jia;Qiao Wang;Xinyu Chen;Anli Wang;Li Zhu;Xiaohui Liu;Lange Zhang;P. Zhuang;J. Jiao;Yu Zhang
中科院分区：
文献类型：
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作者：
Xuzhi Wan;Wei Jia;Qiao Wang;Xinyu Chen;Anli Wang;Li Zhu;Xiaohui Liu;Lange Zhang;P. Zhuang;J. Jiao;Yu Zhang
多酚类抗氧化剂已被建议用于控制热反应过程中丙烯酰胺的生成。然而，它们在保护免受丙烯酰胺毒性方面的作用以及关于生物标志物和代谢组的概况改变的作用机制仍不清楚。共有65名成年人被随机分为茶多酚（TP）组和对照组，并提供薯片，相当于丙烯酰胺的摄入量为12.6 μg/kg·bw，然后是含有200 mg，100 mg或50 mg TP的胶囊或等效安慰剂。此外，丙烯酰胺暴露大鼠的非靶向尿代谢组学分析进行了使用超高效液相色谱与四极杆轨道阱高分辨率质谱。我们的研究结果表明，补充儿茶素促进排泄的N-乙酰基-S-（2-氨甲酰基-2-羟乙基）-L-半胱氨酸在人类和大鼠。我们还发现，表没食子儿茶素没食子酸酯（EGCG）或表儿茶素（EC）的干预减弱了大鼠血液中的血红蛋白加合物的比例的缩水甘油酰胺的血红蛋白加合物的丙烯酰胺。代谢组学分析显示，EGCG/EC干预调控了差异表达的代谢产物，包括1-谷氨酸、2-酮戊二酸、柠檬酸和半胱氨酰甘氨酸。京都基因百科全书和基因组途径分析进一步显示，补充EGCG/EC后，通过糖脂代谢（丙氨酸、天冬氨酸和谷氨酸代谢，以及d-谷氨酰胺和d-谷氨酸代谢）和能量代谢（三羧酸循环）改善了丙烯酰胺诱导的代谢紊乱。值得注意的是，补充使用EGCG通过介导苯丙氨酸代谢中的苯丙氨酸和马尿酸来预防暴露于丙烯酰胺后的心脏代谢风险。在这里，我们通过基于人类和动物研究的代谢谱分析的生物标志物的变化，显示了儿茶素作为主要多酚类抗氧化剂成分对丙烯酰胺毒性的有益作用。这些发现揭示了儿茶素作为天然多酚类抗氧化剂，可能是预防丙烯酰胺诱导的心脏代谢毒性的治疗成分。
Polyphenolic antioxidants have been suggested to control the generation of acrylamide during thermal reactions. However, their role in protecting against the toxicity of acrylamide and the mechanism of action regarding profile alteration of biomarkers and metabolome remains unclear. A total of 65 adults were randomized into tea polyphenols (TP) and control groups and served with potato chips, which corresponded to an intake level of 12.6 μg/kg·bw of acrylamide, followed by capsules containing 200 mg, 100 mg or 50 mg TP, or equivalent placebo. Moreover, nontargeted urinary metabolomics analysis in acrylamide exposed rats was conducted using ultra-high performance liquid chromatography linked with a quadrupole-orbitrap high-resolution mass spectrometry. Our results showed that supplementation with catechins promoted the excretion ofN-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine in both humans and rats. We also found that epigallocatechin gallate (EGCG) or epicatechin (EC) intervention attenuated the ratio of hemoglobin adduct of glycidamide to hemoglobin adduct of acrylamide in rat blood. Metabolomics analysis revealed that EGCG/EC intervention regulated the differential expressed metabolites, includingl-glutamic acid, 2-oxoglutarate, citric acid, and cysteinylglycine. Kyoto Encyclopedia of Genes and Genomes pathway analysis further showed acrylamide-induced metabolic disorders were improved after EGCG/EC supplementation by glycolipid metabolism (alanine, aspartate and glutamate metabolism, andd-Glutamine andd-glutamate metabolism) and energy metabolism (tricarboxylic acid cycle). Notably, the supplement use of EGCG prevented the cardiometabolic risk after exposure to acrylamide by mediating the phenylalanine and hippuric acid in phenylalanine metabolism. Here we showed the beneficial effect of catechins as major polyphenolic antioxidant ingredients on the toxicity of acrylamide by the changes in biomarkers from metabolic profile analysis based on human and animal studies. These findings shed light into the catechins as natural polyphenolic antioxidants that could be a therapeutic ingredient for preventing acrylamide-induced cardiometabolic toxicity.