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


ABSTRACT:

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.

SUBMITTER: Cai Y 

PROVIDER: S-EPMC9636464 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Cai Yueju Y   Li Xiaolan X   Tan Xuying X   Wang Ping P   Zhao Xiaopeng X   Zhang Huayan H   Song Yanyan Y  

Translational pediatrics 20221001 10


<h4>Background</h4>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.<h4>Methods</h4>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 mitocho  ...[more]

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