Antonino Santacroce

Lipid and Protein Oxidation in Newborn Infants after Lutein Administration

Objectives. To test the hypothesis that neonatal supplementation with lutein in the first hours of life reduces neonatal oxidative stress (OS) in the immediate postpartum period. Methods. A randomized controlled, double-blinded clinical trial was conducted among 150 newborns divided into control group, not supplemented (n = 47), and test group, supplemented with lutein on the first day postpartum (n = 103). Blood Samples were collected at birth from cord and at 48 hrs postpartum while routine neonatal metabolic screenings were taking place. Total hydroperoxide (TH), advanced oxidation protein products (AOPP), and biological antioxidant potential (BAP) were measured by spectrophotometry and data were analyzed by Wilcoxon rank sum test and by multivariate logistic regression analysis. Results. Before lutein supplementation, the mean blood concentrations of AOPP, TH, and BAP were 36.10 umol/L, 156.75 mmol/H2O2, and 2361.04 umol/L in the test group. After lutein supplementation, significantly higher BAP increment (0.17 ± 0.22 versus 0.06 versus ± 0.46) and lower TH increment (0.46 ± 0.54 versus 0.34 ± 0.52) were observed in the test group compared to controls. Conclusion. Neonatal supplementation with lutein in the first hours of life increases BAP and reduces TH in supplemented babies compared to those untreated. The generation of free radical-induced damage at birth is reduced by lutein. This trial is registered with ClinicalTrials.gov NCT02068807.

Fetal programming and early identification of newborns at high risk of free radical-mediated diseases

Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.

2-Iminobiotin for the treatment of perinatal asphyxia

Introduction: Perinatal hypoxia–ischemia (HI) continues to be a common underlying cause of brain damage. The outcomes of HI encephalopathy (HIE) are devastating and permanent, making it a major burden for the patient, the family and society. The understanding of the pathways that lead to the injury is vital for finding potential therapies. HI triggers a cascade of several detrimental insults: glutamate-mediated excitotoxicity, nitric oxide (NO) and calcium overload, oxidative stress (OS), stress signaling, inflammation and cell death. Areas covered: The reader will be introduced to the complex biological processes involved in HI injury and how these mechanisms are exploited for current and emerging therapies. Current knowledge on pathways of damage, as well as ongoing experimental therapies are reviewed, based on a comprehensive literature search employing review articles, book chapters and Medline searches. Expert opinion: Recent studies have demonstrated a protective effect of antioxidant drugs against apoptosis after cerebral ischemia and reperfusion. Iminobiotin provides long- and short-term neuroprotection hindering apoptotic pathways. As an antioxidant it acts as NO synthetase inhibitor interrupting the vicious circle and the harmful effects of excessive NO formation. More clinical trials are needed to detect safety and effectiveness of iminobiotin and to establish its dose and optimal time of action.

Oxidative Stress as a Physiological Pain Response in Full-Term Newborns

This research paper aims to investigate if oxidative stress biomarkers increase after a painful procedure in term newborns and if nonpharmacological approaches, or sex, influence pain degree, and the subsequent OS. 83 healthy term newborns were enrolled to receive 10% oral glucose or sensorial saturation (SS) for analgesia during heel prick (HP). The ABC scale was used to score the pain. Advanced oxidation protein products (AOPP) and total hydroperoxides (TH) as biomarkers of OS were measured at the beginning (early-sample) and at the end (late-sample) of HP. The early-sample/late-sample ratio for AOPP and TH was used to evaluate the increase in OS biomarkers after HP. Higher levels of both AOPP and TH ratio were observed in high degree pain (4–6) compared with low degree pain score (0–3) (AOPP: p = 0.049; TH: p = 0.001). Newborns receiving SS showed a significantly lower pain score (p = 0.000) and AOPP ratio levels (p = 0.021) than those without. Males showed higher TH levels at the end of HP (p = 0.005) compared to females. The current study demonstrates that a relationship between pain degree and OS exists in healthy full-term newborns. The amount of OS is gender related, being higher in males. SS reduces pain score together with pain-related OS in the newborns.

The Free Radical Diseases of Prematurity: From Cellular Mechanisms to Bedside

During the perinatal period, free radicals (FRs) are involved in several physiological roles such as the cellular responses to noxia, the defense against infectious agents, the regulation of cellular signaling function, and the induction of a mitogenic response. However, the overproduction of FRs and the insufficiency of an antioxidant mechanism result in oxidative stress (OS) which represents a deleterious process and an important mediator of damage to the placenta and the developing fetus. After birth, OS can be magnified by other predisposing conditions such as hypoxia, hyperoxia, ischemia, hypoxia ischemia-reperfusion, inflammation, and high levels of nonprotein-bound iron. Newborns are particularly susceptible to OS and oxidative damage due to the increased generation of FRs and the lack of adequate antioxidant protection. This impairment of the oxidative balance has been thought to be the common factor of the so-called “free radical related diseases of prematurity,” including retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, kidney damage, and oxidative hemolysis. In this review, we provide an update focused on the factors influencing these diseases refining the knowledge about the role of OS in their pathogenesis and the current evidences of such relationship. Mechanisms governing FR formation and subsequent OS may represent targets for counteracting tissue damage.

The Oxidative Stress in the Fetus and in the Newborn

Free radical (FR) generation is an unavoidable consequence of life in an oxygen-rich atmosphere. FRs can be considered a double-edged sword. Their beneficial effects occur at moderate concentrations and include their physiological roles in cellular responses to noxia, as in defense against infectious agents, in the function of a number of cellular signaling pathways, and in the induction of a mitogenic response. The overproduction of FRs and the insufficiency of antioxidant mechanisms result in oxidative stress (OS), a deleterious process and important mediator of damage to cell structures and tissues. OS can occur before birth as a consequence of hypoxic–ischemic or inflammatory processes and also at birth in all newborns because of the hyperoxic challenge during the transition from the hypoxic intrauterine environment to extrauterine life. During the perinatal period, OS can be magnified by other predisposing conditions such as hyperoxia, hypoxia, ischemia, hypoxia–reperfusion, inflammation, and high levels of non-protein-bound iron (NPBI).