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.

中文翻译：

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麦角硫因调节NF-κB，MAPK和PI3K / AKT信号转导减轻铁超负荷引起的肝细胞损伤

肝脏对铁超负荷引起的氧化损伤高度敏感。麦角硫氨酸是一种硫代组氨酸氨基酸，具有很强的抗氧化剂和金属螯合活性。这项研究旨在探讨麦角硫氨酸对铁触发的肝损伤的潜在调节作用。结果表明，麦角硫因可以抑制铁诱发的炎症和细胞凋亡，肿瘤坏死因子-α和白介素-6水平以及caspase-3活性显着降低证明了这一点。如调节磷脂酰肌醇3-激酶/蛋白激酶B信号所示，麦角硫因可显着改善肝细胞存活率。与减少坏死细胞死亡一致，麦角硫因减少了铁引起的组织病理学改变，并降低了肝酶的血清活性。机械上，麦角硫因减少了核因子kappa B p65的核易位并调节了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，这些结果指出，麦角硫因对铁诱发的肝细胞损伤的调节作用可能是通过抗炎，抗氧化剂和可能的铁螯合能力介导的。