In the present study, we demonstrate the coaction of thioredoxin and glutathione (GSH) systems in mouse liver against iron overload‐induced oxidative stress (OS). Mice were injected intraperitoneally with an iron dextran solution twice a week for 3 weeks. Iron accumulation in mouse liver was demonstrated spectroscopically. To confirm the iron overload model in the liver, the increased gene expression levels of hepcidin (Hamp), ferroportin (Fpn1), and ferritin (Fth1), which regulate iron trafficking, were observed by a quantitative polymerase chain reaction. In the case of iron overload, the GSH level and the reduced glutathione/oxidized glutathione ratio, which represents a marker of OS, decreased significantly. An increase in the malondialdehyde level, one of the final products of the lipid peroxidation process, was observed. The gene expression of the thioredoxin system, including thioredoxin (Trx1) and thioredoxin reductase (TrxR1), was examined. Though TrxR1 expression decreased, no changes were observed in Trx1. The enzyme activity and semiquantitative protein expression of TRXR1 increased. The activity of GSH reductase and GSH peroxidase increased in the iron overload group. The gene and protein expressions of thioredoxininteracting protein, which is an indicator of the commitment of the cell to apoptosis, were elevated significantly. The increased protein expression of Bcl‐2‐related X protein and CASPASE‐3, which is an indicator of apoptosis, increased significantly. In conclusion, excess iron accumulation in mouse liver tissue causes OS, which affects the redox state of the thioredoxin and GSH systems, inducing cell apoptosis and also ferroptosis due to increased lipid peroxidation and the depletion of GSH level.

中文翻译：

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肝硫氧还蛋白和谷胱甘肽系统在铁超载引起的氧化应激中的相互作用

在本研究中，我们证明了硫氧还蛋白和谷胱甘肽（GSH）系统在小鼠肝脏中对抗铁超负荷引起的氧化应激（OS）的相互作用。每周两次向小鼠腹膜内注射右旋糖酐铁溶液，持续3周。用光谱法证明了小鼠肝脏中铁的蓄积。为了确认在肝，铁调素的增加的基因表达水平（该铁超负荷模型HAMP），膜铁转运蛋白（Fpn1）和铁蛋白（FTH1通过定量聚合酶链反应观察到调节铁运输的β-内酰胺酶。在铁过载的情况下，GSH水平和代表OS的谷胱甘肽/氧化型谷胱甘肽比值的降低显着降低。观察到丙二醛水平增加，脂质过氧化过程的终产物之一。检查了包括硫氧还蛋白（Trx1）和硫氧还蛋白还原酶（TrxR1）在内的硫氧还蛋白系统的基因表达。尽管 TrxR1表达下降，但在Trx1中未观察到变化。TRXR1的酶活性和半定量蛋白表达增加。铁超负荷组中谷胱甘肽还原酶和谷胱甘肽过氧化物酶的活性增加。硫氧还蛋白相互作用蛋白的基因和蛋白表达显着升高，这是细胞对细胞凋亡的承诺的指标。Bcl-2相关X蛋白和CASPASE-3的蛋白表达增加，这是细胞凋亡的指标，其表达明显增加。总之，小鼠肝脏组织中过量的铁蓄积会导致OS，这会影响硫氧还蛋白和GSH系统的氧化还原状态，并由于脂质过氧化作用增加和GSH耗竭而导致细胞凋亡以及肥大病。