Vitamin D suppresses ferroptosis and protects against neonatal hypoxic-ischemic encephalopathy by activating the Nrf2/HO-1 pathway
| Autor: | Yueju, Cai, Xiaolan, Li, Xuying, Tan, Ping, Wang, Xiaopeng, Zhao, Huayan, Zhang, Yanyan, Song |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Translational Pediatrics. 11:1633-1644 |
| ISSN: | 2224-4344 2224-4336 |
| Popis: | Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death, and vitamin D (VD) is a neuroprotection nutrition whose deficiency is associated with its risk. However, the mechanism of VD involved in neonatal HIE is not well known.In this experiment a hypoxic-ischemic brain damage (HIBD) model was established by using the Rice-Vannucci method, rats were intraperitoneally injected with 0.1 µg/kg VD every day for two weeks. The brain damage and mitochondria injury were examined by hematoxylin-eosin (HE) staining and transmission electron microscope (TEM), respectively. The oxidation response and inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA), and the cell viability was determined by Cell Counting Kit-8 (CCK-8). mRNA and protein expression were detected by quantitative real real-time PCR (qRT-PCR), Western blot, and immunofluorescence.The results showed VD effectively ameliorated brain histologic damage and mitochondria injury induced by hypoxic ischemia (HI). VD elevated the expression of Nrf2 and HO-1, which resulted in increased levels of GPX4, superoxide dismutase (SOD), and glutathione (GSH) and reduced content of malondialdehyde (MDA) and reactive oxygen species (ROS), resulting in decreased ferroptosis in HI-treated rats. Moreover, VD reduced the secretion of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β.VD suppresses ferroptosis through activation of the Nrf2/HO-1 signaling pathway and exerts a protective role in neonatal HIE. |
| Databáze: | OpenAIRE |
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