Oxygen radical disease in the newborn, revisited: Oxidative stress and disease in the newborn period

Abstract

Thirty years ago, there was an emerging appreciation for the significance of oxidative stress in newborn disease. This prompted a renewed interest in the impact of oxygen therapy for the newborn in the delivery room and beyond, especially in premature infants. Today, the complexity of oxidative stress both in normal regulation and pathology is better understood, especially as it relates to neonatal mitochondrial oxidative stress responses to hyperoxia. Mitochondria are recipients of oxidative damage and have a propensity for oxidative self-injury that has been implicated in the pathogenesis of neonatal lung diseases. Similarly, both intrauterine growth restriction (IUGR) and macrosomia are associated with mitochondrial dysfunction and oxidative stress. Additionally, reoxygenation with 100% O2 in a hypoxic-ischemic newborn lamb model increased the production of pro-inflammatory cytokines in the brain. Moreover, the interplay between inflammation and oxidative stress in the newborn is better understood because of animal studies. Transcriptomic analyses have found a number of genes to be differentially expressed in murine models of bronchopulmonary dysplasia (BPD). Epigenetic changes have also been detected both in animal models of BPD and premature infants exposed to oxygen. Antioxidant therapy to prevent newborn disease has not been very successful; however, new therapeutic principles, like melatonin, are under investigation.

Maternal Diabetes Mellitus and Persistent Pulmonary Hypertension of the Newborn: Accumulated Evidence From Observational Studies

“…In our research, we further found that maternal diabetes was also associated with PPHN. Newborn infants are at risk of oxidative stress after transitioning from the low oxygen environment, the uterus, to air (30). This process may be exacerbated by maternal diabetes mellitus, for the causal link between diabetic hyperglycemia and the production of reactive oxygen species (ROS) by mitochondria (31).…”

“…Oxidative stress has been recognized as a critical factor in the pathophysiology of PPHN (30). In lamb with PPHN induced by antenatal ligation of ductus arteriosus, the endothelium and vascular smooth muscle of the pulmonary arteries showed an elevated level of superoxide and H 2 O 2 (37), with decreased expression and activity in manganese SOD (38).…”

“…However, ROS alters nitric oxide signalling pathways. The former decreased expression of eNOS and soluble guanylate cyclase activates PDE5 (30). H 2 O 2 has also been linked to the decreased activity of extracellular SOD (30).…”

“…The former decreased expression of eNOS and soluble guanylate cyclase activates PDE5 (30). H 2 O 2 has also been linked to the decreased activity of extracellular SOD (30). Moreover, the generation of nitric oxide from its precursor l-arginine by eNOS requires the presence of several cofactors, in particular, tetrahydrobiopterin (41).…”

Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1

“…Numerous studies have been performed to investigate the efficacy of antioxidant therapies in preventing acute inflammatory injuries and ARDS. However, to date, there is no FDA approved treatment for patients receiving mechanical ventilation and hyperoxia who develop ALI/ARDS [39,40]. Recently, research has been directed toward dietary antioxidants, such as vitamin C and Nrf2-inducers.…”