Division of Biochemistry, Department of Pharmacology, College of Pharmacy, Taif University, Taif, Saudi Arabia.
Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
J Biochem Mol Toxicol. 2021 May;35(5):e22729. doi: 10.1002/jbt.22729. Epub 2021 Feb 13.
The liver is highly susceptible to iron overload-evoked oxidative injury. Ergothioneine is a thio-histidine amino acid that has exhibited strong antioxidant and metal chelating activities. This study aimed at exploring the potential modulating effects of ergothioneine on iron-triggered liver injury. The results showed that ergothioneine inhibited iron-evoked inflammation and apoptosis as demonstrated by a significant reduction in tumor necrosis factor-α and interleukin-6 levels and in caspase-3 activity. Ergothioneine significantly improved liver cell survival as indicated by modulating phosphatidylinositol 3-kinase/protein kinase B signaling. Consistent with reduced necrotic cell death, ergothioneine diminished the iron-evoked histopathological changes and decreased serum activity of the liver enzymes. Mechanistically, ergothioneine reduced nuclear translocation of nuclear factor kappa B p65 and modulated p38 mitogen-activated protein kinase/c-Fos signaling. In addition, it enhanced the liver tissue antioxidant potential and curbed hepatic iron load. Together, these results point out the modulatory effects of ergothioneine on iron-evoked liver cell injury that are possibly mediated via anti-inflammatory, antioxidant, and possible iron chelation capabilities.
肝脏极易受到铁过载引起的氧化损伤。麦硫因是一种含硫的组氨酸氨基酸，具有很强的抗氧化和金属螯合活性。本研究旨在探讨麦硫因对铁触发的肝损伤的潜在调节作用。结果表明，麦硫因抑制了铁引起的炎症和细胞凋亡，肿瘤坏死因子-α和白细胞介素-6 水平以及半胱天冬酶-3 活性显著降低。麦硫因通过调节磷脂酰肌醇 3-激酶/蛋白激酶 B 信号转导显著改善了肝细胞的存活。与坏死细胞死亡减少一致，麦硫因减轻了铁引起的组织病理学变化，并降低了血清中肝脏酶的活性。其机制为，麦硫因减少了核因子 kappa B p65 的核转位，并调节了 p38 丝裂原活化蛋白激酶/c-Fos 信号转导。此外，它增强了肝脏组织的抗氧化能力，并抑制了肝铁负荷。总之，这些结果表明，麦硫因对铁诱导的肝细胞损伤具有调节作用，其机制可能是通过抗炎、抗氧化和可能的铁螯合能力介导的。
