Kose Tugba, Moreno-Fernandez Jorge, Vera-Aviles Mayra, Sharp Paul A, Latunde-Dada Gladys O
Department of Nutritional Sciences, School of Life Course and Population Sciences, King's College London, Franklin-Wilkins-Building, 150 Stamford Street, London, SE1 9NH, UK.
Department of Physiology, University of Granada, 18071, Granada, Spain.
Biochem Biophys Rep. 2023 Jul 31;35:101521. doi: 10.1016/j.bbrep.2023.101521. eCollection 2023 Sep.
Liver as iron storage organ is particularly susceptible to oxidative stress-induced injury from excess iron. Thus, antioxidant therapies are often used to reverse oxidative damage and protect cells and tissues. This study investigated the protective effects of phenolic acids; ferulic acid (FA) and its metabolite, ferulic acid 4-O-sulfate disodium salt (FAS) against oxidative stress under iron overload conditions in mouse and HepG2 cells. Cells were exposed to FA or FAS and then treated with iron-induced oxidative stress complex of 50 μmol/L FAC and 20 μmol/L of 8-hydroxyquinoline 8HQ (8HQ-FAC). Iron dextran was injected intraperitoneally on alternate days for 10 days to induce the iron overload condition in BALB/c mice. The study revealed that the phenolic acids were protective against ROS production, lipid peroxidation and antioxidant depletion in HepG2 cells and liver tissues of BALB/c mice during iron-induced oxidative stress. The protective function of phenolic acids was achieved by the transcriptional activation of nuclear factor erythroid-2-related factor 2 (Nrf2) to regulate antioxidant genes. In conclusion, the study provides evidence that FA has the potential as a therapeutic agent against iron-related diseases such as T2D.
肝脏作为铁储存器官，特别容易受到过量铁引起的氧化应激损伤。因此，抗氧化疗法常被用于逆转氧化损伤并保护细胞和组织。本研究调查了酚酸（阿魏酸（FA）及其代谢产物阿魏酸4-O-硫酸二钠盐（FAS））在小鼠和HepG2细胞铁过载条件下对氧化应激的保护作用。细胞先暴露于FA或FAS，然后用50μmol/L FAC和20μmol/L 8-羟基喹啉8HQ（8HQ-FAC）的铁诱导氧化应激复合物处理。每隔一天腹腔注射右旋糖酐铁，持续10天，以诱导BALB/c小鼠出现铁过载情况。研究表明，在铁诱导的氧化应激期间，酚酸对HepG2细胞和BALB/c小鼠肝脏组织中的活性氧生成、脂质过氧化和抗氧化剂消耗具有保护作用。酚酸的保护功能是通过核因子红细胞2相关因子2（Nrf2）的转录激活来调节抗氧化基因实现的。总之，该研究提供了证据表明FA有潜力作为治疗与铁相关疾病（如2型糖尿病）的治疗剂。
