Collaborative Innovation Center for Modern Grain Circulation and Safety, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China.
Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China.
Molecules. 2023 Jun 30;28(13):5132. doi: 10.3390/molecules28135132.
Acrylamide (ACR) is produced under high-temperature cooking of carbohydrate-rich foods via the Maillard reaction. It has been reported that ACR has hepatic toxicity and can induce liver circadian disorder. A high fat diet (HFD) could dysregulate liver detoxification. The current study showed that administration of ACR (100 mg/kg) reduced the survival rate in HFD-fed mice, which was more pronounced when treated during the night phase than during the day phase. Furthermore, ACR (25 mg/kg) treatment could cause chronotoxicity in mice fed a high-fat diet, manifested as more severe mitochondrial damage of liver during the night phase than during the day phase. Interestingly, HFD induced a higher CYP2E1 expressions for those treated during the night phase, leading to more severe DNA damage. Meanwhile, the expression of gut tight junction proteins also significantly decreases at night phase, leading to the leakage of LPSs and exacerbating the inflammatory response at night phase. These results indicated that a HFD could induce the chronotoxicity of ACR in mice liver, which may be associated with increases in CYP2E1 expression in the liver and gut leak during the night phase.
丙烯酰胺（ACR）是在高温烹饪富含碳水化合物的食物时通过美拉德反应产生的。据报道，丙烯酰胺具有肝毒性，并可诱导肝脏昼夜节律紊乱。高脂肪饮食（HFD）可扰乱肝脏的解毒功能。本研究表明，ACR（100mg/kg）的给药降低了高脂肪饮食喂养的小鼠的存活率，在夜间给药比在白天给药时更为明显。此外，ACR（25mg/kg）处理可导致高脂肪饮食喂养的小鼠出现时间毒性，表现为夜间肝脏的线粒体损伤比白天更严重。有趣的是，HFD 诱导夜间给药的 CYP2E1 表达升高，导致更严重的 DNA 损伤。同时，夜间紧密连接蛋白的表达也显著降低，导致 LPS 渗漏，并加重夜间的炎症反应。这些结果表明，HFD 可诱导 ACR 在小鼠肝脏中的时间毒性，这可能与肝脏和肠道在夜间 CYP2E1 表达增加和渗漏增加有关。
