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.
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