College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China; College of Animal Science and Technology, Zhejiang Agriculture and Forestry University, Hangzhou, China.
College of Food Science and Technology, Nanjing Agricultural University, Nanjing, China.
Ecotoxicol Environ Saf. 2021 Jan 15;208:111543. doi: 10.1016/j.ecoenv.2020.111543. Epub 2020 Nov 9.
Acrylamide (ACR) is generated during thermal processing of carbohydrate-rich foods at high temperature and can directly enter the body through ingestion, inhalation and skin contact. The toxicity of ACR has been widely studied. The main results of these studies show that exposure to ACR can cause neurotoxicity in both animals and humans, and show reproductive toxicity and carcinogenicity in rodent animal models. However, the mechanism of toxicity of ACR has not been studied by metabolomics approaches, and the effect of ACR on autophagy remains unknown. Here, UOS cell were treated with ACR 6 and 24 h and collected for further study. We have demonstrated that ACR inhibited autophagic flux, and increased ROS content. Accumulation of ROS resulted in increase of apoptosis rates and secretion of inflammatory factors. In addition, significant differences in metabolic profiles were observed between ACR treated and control cells according to multiple analysis models. A total of 73 key differential metabolites were identified. They were involved in multiple metabolic pathways. Among them, exposure to ACR caused glycolysis/gluconeogenesis attenuation by decreasing levels of glycolytic intermediates, reduced the rate of the TCA cycle, while elevating levels of several amino acid metabolites and lipid metabolites. In summary, our study provides useful evidence of cytotoxicity caused by ACR via metabolomics and multiple bioanalytic methods.
丙烯酰胺（ACR）在高温下富含碳水化合物的食物的热加工过程中产生，可通过摄入、吸入和皮肤接触直接进入人体。ACR 的毒性已得到广泛研究。这些研究的主要结果表明，暴露于 ACR 可导致动物和人类的神经毒性，并在啮齿动物动物模型中表现出生殖毒性和致癌性。然而，ACR 的毒性机制尚未通过代谢组学方法进行研究，ACR 对自噬的影响仍不清楚。在这里，用 ACR 处理 UOS 细胞 6 和 24 小时并收集进行进一步研究。我们已经证明 ACR 抑制自噬通量，并增加 ROS 含量。ROS 的积累导致细胞凋亡率和炎症因子分泌增加。此外，根据多种分析模型，观察到 ACR 处理和对照细胞之间的代谢谱存在显著差异。共鉴定出 73 个关键差异代谢物。它们涉及多种代谢途径。其中，ACR 暴露通过降低糖酵解中间产物的水平，降低糖酵解/糖异生的速度，同时提高几种氨基酸代谢物和脂质代谢物的水平，从而导致三羧酸循环速率降低。总之，我们的研究通过代谢组学和多种生物分析方法为 ACR 引起的细胞毒性提供了有用的证据。
