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Vitamin D suppresses ferroptosis and protects against neonatal hypoxic-ischemic encephalopathy by activating the Nrf2/HO-1 pathway

BACKGROUND: 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. METHODS: In this experiment a hypoxic-ischemi...

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Detalles Bibliográficos
Autores principales: Cai, Yueju, Li, Xiaolan, Tan, Xuying, Wang, Ping, Zhao, Xiaopeng, Zhang, Huayan, Song, Yanyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636464/
https://www.ncbi.nlm.nih.gov/pubmed/36345441
http://dx.doi.org/10.21037/tp-22-397
Descripción
Sumario:BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: VD suppresses ferroptosis through activation of the Nrf2/HO-1 signaling pathway and exerts a protective role in neonatal HIE.