Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
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. |
---|