Hyperoxia Induces Ferroptosis and Impairs Lung Development in Neonatal Mice

Abstract

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.