State Key Laboratory of Food Science and Technology, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, Nanchang 330047, China.
J Agric Food Chem. 2023 May 17;71(19):7427-7439. doi: 10.1021/acs.jafc.3c01378. Epub 2023 May 3.
Acrylamide (ACR) generated in carbohydrate-rich foods during thermal processing has been demonstrated to exhibit hepatotoxicity. As one of the most consumed flavonoids with diet, quercetin (QCT) possesses the ability to protect against ACR-induced toxicity, albeit its mechanism is unclear. Herein, we discovered that QCT alleviated ACR-induced elevated levels of reactive oxygen species (ROS), AST, and ALT in mice. RNA-seq analysis revealed that QCT reversed the ferroptosis signaling pathway upregulated by ACR. Subsequently, experiments indicated that QCT inhibited ACR-induced ferroptosis through the reduction of oxidative stress. With autophagy inhibitor chloroquine, we further confirmed that QCT suppressed ACR-induced ferroptosis by inhibiting oxidative stress-driven autophagy. Additionally, QCT specifically reacted with autophagic cargo receptor NCOA4, blocked the degradation of iron storage protein FTH1, and eventually downregulated the intracellular iron levels and the consequent ferroptosis. Collectively, our results presented a unique approach to alleviate ACR-induced liver injury by targeting ferroptosis with QCT.
丙烯酰胺（ACR）在富含碳水化合物的食物在热加工过程中产生，已被证明具有肝毒性。槲皮素（QCT）作为饮食中最消耗的类黄酮之一，具有抵御 ACR 诱导的毒性的能力，尽管其机制尚不清楚。在这里，我们发现 QCT 减轻了 ACR 诱导的小鼠活性氧（ROS）、AST 和 ALT 水平升高。RNA-seq 分析显示，QCT 逆转了 ACR 上调的铁死亡信号通路。随后的实验表明，QCT 通过降低氧化应激抑制了 ACR 诱导的铁死亡。用自噬抑制剂氯喹，我们进一步证实 QCT 通过抑制氧化应激驱动的自噬来抑制 ACR 诱导的铁死亡。此外，QCT 特异性地与自噬货物受体 NCOA4 反应，阻止铁储存蛋白 FTH1 的降解，最终降低细胞内铁水平和随后的铁死亡。总的来说，我们的结果提出了一种通过用 QCT 靶向铁死亡来减轻 ACR 诱导的肝损伤的独特方法。
