State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, PR China.
Department of Environmental Science, School of Engineering, China Pharmaceutical University, Nanjing 211198, PR China.
Sci Total Environ. 2021 May 15;769:144849. doi: 10.1016/j.scitotenv.2020.144849. Epub 2021 Jan 19.
The toxicity of arsenic (As) can be influenced by many nutrients in food. However, the combined effects and underlying mechanisms of As and palmitic acid (PA) are still unclear. Here, cell viability, oxidative stress, lipids accumulation, gene expression profiles, and metabolome profiles of human hepatoma HepG2 cells exposed to As, PA, and As + PA were analyzed and compared. Results showed that co-exposure of 100 μM PA and 2 μM As induced lower cell viability, higher intracellular reactive oxygen species level, more lipid droplet accumulation, and more intracellular triglyceride contents than As alone or PA alone exposure. High-throughput quantitative PCR and H NMR-based metabolomics analysis showed that co-exposure of As and PA caused all toxic effects on gene expression and metabolome profiles induced by As alone or PA alone exposure, and showed higher toxicities. Gene expression profiles in the As + PA group had higher similarity with those in the As group than the PA group. However, PA played a more important role in metabolism disorder than As in their interactive effects. Oxidative stress and lipid metabolism disorder were found to be the main toxic effects in the As + PA group. Several differentially expressed genes (such as OXR1, OXSR1, INSR, and PPARA) and changed metabolites (such as pyruvate, acetate, and L-phenylalanine) were involved in the combined toxicity of As and PA. This study provides basic information on the interactive effects of As and PA, which is useful for the health risk assessment of As and FFA.
砷（As）的毒性可受食物中许多营养物质的影响。然而，As 和棕榈酸（PA）的联合作用及其潜在机制仍不清楚。本研究分析并比较了暴露于 As、PA 和 As + PA 的人肝癌 HepG2 细胞的细胞活力、氧化应激、脂质积累、基因表达谱和代谢组谱。结果表明，与单独暴露于 As 或 PA 相比，100 μM PA 和 2 μM As 的共暴露诱导较低的细胞活力、更高的细胞内活性氧水平、更多的脂滴积累和更高的细胞内甘油三酯含量。高通量定量 PCR 和基于 H NMR 的代谢组学分析表明，As 和 PA 的共暴露导致 As 或 PA 单独暴露引起的基因表达和代谢组谱的所有毒性作用，并表现出更高的毒性。As + PA 组的基因表达谱与 As 组的相似性高于 PA 组。然而，在它们的相互作用中，PA 在代谢紊乱方面比 As 发挥更重要的作用。氧化应激和脂质代谢紊乱被发现是 As + PA 组的主要毒性作用。一些差异表达基因（如 OXR1、OXSR1、INSR 和 PPARA）和代谢物（如丙酮酸、乙酸和 L-苯丙氨酸）参与了 As 和 PA 的联合毒性作用。本研究为 As 和 FFA 的健康风险评估提供了 As 和 PA 相互作用的基础信息。
