Se/Albumin Nanoparticles for Inhibition of Ferroptosis in Tubular Epithelial Cells during Acute Kidney Injury
Se/Albumin Nanoparticles for Inhibition of Ferroptosis in Tubular Epithelial Cells during Acute Kidney Injury
复制标题
硒/白蛋白纳米颗粒抑制急性肾损伤期间管状上皮细胞铁死亡
DOI：
10.1021/acsanm.1c02706
复制
发表时间：
2022-01-16
影响因子：
5.9
通讯作者：
Cao, Ke
中科院分区：
文献类型：
--
作者：
Deng, Liping;Xiao, Mengqing;Cao, Ke
顺铂（DDP）是一种广泛使用的化疗药物，在治疗多种肿瘤中发挥着不可替代的作用。然而，找到 DDP 介导的肾损伤的解决方案和替代方案至关重要。这种急性肾损伤（AKI）的特点是铁死亡的发生，铁死亡被定义为由过度脂质过氧化介导的铁催化的调节性坏死。为了解决这个问题，我们专注于纳米颗粒的潜在功能，设计出一种新技术来预防 DDP 引起的肾损伤。含有微量元素硒的硒纳米粒子（Se NPs）已被证明具有很强的抗氧化性。然而，Se NPs 治疗 DDP 引起的肾损伤的能力在很大程度上仍未得到探索。在这里，我们利用小鼠模型详细阐述了我们自主开发的 Se/Albumin 纳米颗粒（Se/Albumin NPs、SA NPs）在减轻 DDP 诱导的急性肾损伤中的作用。患有急性肾损伤（AKI）的小鼠肾功能明显受损，体重减轻。苏木精-伊红染色（H&E）和高碘酸-希夫（PAS）染色用于确定肾小管形态变化的程度，结果显示严重的间质水肿。进一步的研究显示，电子显微镜下肾小管组织和细胞中丙二醛（MDA）增加，超氧化物歧化酶（SOD）减少，谷胱甘肽（GSH）和谷胱甘肽过氧化物酶（GPx）水平降低，从而表明促凋亡变化。此外，铁死亡相关蛋白谷胱甘肽过氧化物酶 4 (GPX4) 和铁转运蛋白 1 (FPN1) 的水平降低，而转铁蛋白和 ACSL4 的水平升高。我们的研究表明，SA 纳米颗粒比 Se 纳米颗粒在改善这些损害方面更有效。总之，结果表明 SA NPs 通过抑制铁死亡来减少 DDP 诱导的 AKI，表明 SA NPs 在急性肾损伤中具有潜在的治疗作用。
Cisplatin (DDP) is a widely used chemotherapeutic agent that plays an unsubstitutable role in treating various tumors. However, it is crucial to identify solutions and alternatives for DDP-mediated renal injury. This acute kidney injury (AKI) is characterized by the occurrence of ferroptosis, which is defined as an iron-catalyzed regulatory necrosis mediated by excessive lipid peroxidation. To solve this problem, we concentrate on the potential function of nanoparticles to devise a new technique to prevent DDP-induced kidney injury. Selenium nanoparticles (Se NPs) containing the trace element, selenium, have been shown to exhibit strong oxidation resistance. However, the ability of Se NPs to treat DDP-induced kidney injury remains largely unexplored. Here, we elaborate the role of our self-developed Se/Albumin nanoparticles (Se/Albumin NPs, SA NPs) in alleviating DDP-induced acute kidney damage using a murine model. Mice with acute kidney injury (AKI) had significantly impaired renal function and reduced body weight. Hematoxylin-eosin staining (H&E) and periodic acid-Schiff (PAS) staining, which was carried out to determine the extent of the morphological changes in renal tubules, revealed severe interstitial edema. Further studies revealed an increase in malonaldehyde (MDA), a decrease in superoxide dismutase (SOD), and reduced glutathione (GSH) and glutathione peroxidase (GPx) levels in the renal tubule tissues and cells under an electron microscope, thereby indicating pro-apoptotic changes. Moreover, the levels of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) andferroportin1 (FPN1) decreased while those of transferrin and ACSL4 increased. Our study reveals that SA NPs are more potent at ameliorating these damages than Se NPs. In all, the results suggest that the SA NPs reduce DDP-induced AKI by inhibiting ferroptosis, indicating the potential therapeutic role of SA NPs in acute renal damage.