The role of ferroptosis in DM-induced liver injury

IF 4.1 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biometals Pub Date : 2024-06-14 DOI:10.1007/s10534-024-00600-6
Keping Wu, Jiasi Chen, Jiawen Lin, Enyi Zhu, Xiaochang Xu, Xiuhong Yan, Lang Ju, Mingcheng Huang, Yimin Zhang
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Abstract

The liver damage caused by Diabetes Mellitus (DM) has attracted increasing attention in recent years. Liver injury in DM can be caused by ferroptosis, a form of cell death caused by iron overload. However, the role of iron transporters in this context is still not clear. Herein, we attempted to shed light on the pathophysiological mechanism of ferroptosis. DM was induced in 8-week-old male rats by streptozotocin (STZ) before assessment of the degree of liver injury. Together with histopathological changes, variations in glutathione peroxidase 4 (GPX4), glutathione (GSH), superoxide dismutase (SOD), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), ferritin light chain (FTL), ferroportin and Prussian blue staining, were monitored in rat livers before and after treatment with Fer-1. In the liver of STZ-treated rats, GSH and SOD levels decreased, whereas those of malondialdehyde (MDA) increased. Expression of TFR1, FTH and FTL increased whereas that of glutathione peroxidase 4 (GPX4) and ferroportin did not change significantly. Prussian blue staining showed that iron levels increased. Histopathology showed liver fibrosis and decreased glycogen content. Fer-1 treatment reduced iron and MDA levels but GSH and SOD levels were unchanged. Expression of FTH and FTL was reduced whereas that of ferroportin showed a mild decrease. Fer-1 treatment alleviated liver fibrosis, increased glycogen content and mildly improved liver function. Our study demonstrates that ferroptosis is involved in DM-induced liver injury. Regulating the levels of iron transporters may become a new therapeutic strategy in ferroptosis-induced liver injury.

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铁蛋白沉积在 DM 引起的肝损伤中的作用
近年来,糖尿病(DM)引起的肝损伤日益受到关注。DM的肝损伤可由铁中毒引起,铁中毒是铁超载导致的一种细胞死亡形式。然而,铁转运体在其中的作用仍不明确。在此,我们试图揭示铁变态反应的病理生理机制。在评估肝损伤程度之前,先用链脲佐菌素(STZ)诱导 8 周大的雄性大鼠发生 DM。在使用 Fer-1 治疗前后,大鼠肝脏中的谷胱甘肽过氧化物酶 4 (GPX4)、谷胱甘肽 (GSH)、超氧化物歧化酶 (SOD)、转铁蛋白受体 1 (TFR1)、铁蛋白重链 (FTH)、铁蛋白轻链 (FTL)、铁蛋白和普鲁士蓝染色的变化与组织病理学变化一起被监测。在 STZ 处理的大鼠肝脏中,GSH 和 SOD 水平下降,而丙二醛(MDA)水平上升。TFR1、FTH和FTL的表达量增加,而谷胱甘肽过氧化物酶4(GPX4)和铁蛋白的表达量没有明显变化。普鲁士蓝染色显示铁含量增加。组织病理学显示肝纤维化和糖原含量降低。Fer-1 治疗降低了铁和 MDA 水平,但 GSH 和 SOD 水平没有变化。FTH 和 FTL 的表达量减少,而铁蛋白的表达量则轻度下降。Fer-1 治疗缓解了肝纤维化,增加了糖原含量,并轻度改善了肝功能。我们的研究表明,铁蛋白沉积参与了 DM 诱导的肝损伤。调节铁转运体的水平可能成为治疗铁变态反应诱导的肝损伤的一种新策略。
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来源期刊
Biometals
Biometals 生物-生化与分子生物学
CiteScore
5.90
自引率
8.60%
发文量
111
审稿时长
3 months
期刊介绍: BioMetals is the only established journal to feature the important role of metal ions in chemistry, biology, biochemistry, environmental science, and medicine. BioMetals is an international, multidisciplinary journal singularly devoted to the rapid publication of the fundamental advances of both basic and applied research in this field. BioMetals offers a forum for innovative research and clinical results on the structure and function of: - metal ions - metal chelates, - siderophores, - metal-containing proteins - biominerals in all biosystems. - BioMetals rapidly publishes original articles and reviews. BioMetals is a journal for metals researchers who practice in medicine, biochemistry, pharmacology, toxicology, microbiology, cell biology, chemistry, and plant physiology who are based academic, industrial and government laboratories.
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