TY - JOUR
T1 - Hyperoxia Induces Ferroptosis and Impairs Lung Development in Neonatal Mice
AU - Chou, Hsiu Chu
AU - Chen, Chung Ming
N1 - Funding Information:
Funding: This work was supported by a grant from Taipei Medical University Hospital (111TMUH-MOST-15), Taipei, Taiwan.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4
Y1 - 2022/4
N2 - Oxygen is often required to treat newborns with respiratory disorders, and prolonged exposure to high oxygen concentrations impairs lung development. Ferroptosis plays a vital role in the development of many diseases and has become the focus of treatment and prognosis improve-ment for related diseases, such as neurological diseases, infections, cancers, and ischemia-reperfu-sion injury. Whether ferroptosis participates in the pathogenesis of hyperoxia-induced lung injury remains unknown. The aims of this study are to determine the effects of hyperoxia on lung ferrop-tosis and development in neonatal mice. Newborn C57BL/6 mice were reared in either room air (RA) or hyperoxia (85% O2) at postnatal days 1–7. On postnatal days 3 and 7, the lungs were har-vested for histological and biochemical analysis. The mice reared in hyperoxia exhibited significantly higher Fe2+, malondialdehyde, and iron deposition and significantly lower glutathione, glu-tathione peroxidase 4, and vascular density than did those reared in RA on postnatal days 3 and 7. The mice reared in hyperoxia exhibited a comparable mean linear intercept on postnatal day 3 and a significantly higher mean linear intercept than the mice reared in RA on postnatal day 7. These findings demonstrate that ferroptosis was induced at a time point preceding impaired lung devel-opment, adding credence to the hypothesis that ferroptosis is involved in the pathogenesis of hy-peroxia-induced lung injury and suggest that ferroptosis inhibitors might attenuate hyperoxia-in-duced lung injury.
AB - Oxygen is often required to treat newborns with respiratory disorders, and prolonged exposure to high oxygen concentrations impairs lung development. Ferroptosis plays a vital role in the development of many diseases and has become the focus of treatment and prognosis improve-ment for related diseases, such as neurological diseases, infections, cancers, and ischemia-reperfu-sion injury. Whether ferroptosis participates in the pathogenesis of hyperoxia-induced lung injury remains unknown. The aims of this study are to determine the effects of hyperoxia on lung ferrop-tosis and development in neonatal mice. Newborn C57BL/6 mice were reared in either room air (RA) or hyperoxia (85% O2) at postnatal days 1–7. On postnatal days 3 and 7, the lungs were har-vested for histological and biochemical analysis. The mice reared in hyperoxia exhibited significantly higher Fe2+, malondialdehyde, and iron deposition and significantly lower glutathione, glu-tathione peroxidase 4, and vascular density than did those reared in RA on postnatal days 3 and 7. The mice reared in hyperoxia exhibited a comparable mean linear intercept on postnatal day 3 and a significantly higher mean linear intercept than the mice reared in RA on postnatal day 7. These findings demonstrate that ferroptosis was induced at a time point preceding impaired lung devel-opment, adding credence to the hypothesis that ferroptosis is involved in the pathogenesis of hy-peroxia-induced lung injury and suggest that ferroptosis inhibitors might attenuate hyperoxia-in-duced lung injury.
KW - glutathione
KW - glutathione peroxidase 4
KW - hyperoxia
KW - malondialdehyde
KW - mean linear inter-cept
KW - von Willebrand factor
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U2 - 10.3390/antiox11040641
DO - 10.3390/antiox11040641
M3 - Article
AN - SCOPUS:85127197296
SN - 2076-3921
VL - 11
JO - Antioxidants
JF - Antioxidants
IS - 4
M1 - 641
ER -