The Multiple Facets of Lutein: A Call for Further Investigation in the Perinatal Period

Lutein may have important antioxidant actions in free-radical-mediated diseases, in addition to its well-known antioxidant and cytoprotective effects on macula and photoreceptors. The peculiar perinatal susceptibility to oxidative stress indicates that prophylactic use of antioxidants as lutein could help to prevent or at least to reduce oxidative stress related diseases in newborns. Since lutein is not synthesized by humans, the intake primarily depends on diet or supplementation. Newborns receive lutein exclusively from breast milk. Lutein supplementation in term newborns has been reported to reduce oxidative stress and increase antioxidant capacities in the first days of life. Innovative frontiers concerning lutein supplementation are orientated toward cardiometabolic health improvement and cognitive benefits. The safety of lutein as an antioxidant agent has been confirmed in experimental and clinical studies, but its routine use is not recommended in perinatal period. This review summarizes what is known about the role of lutein as an antioxidant and anti-inflammatory agent in animal model and humans

New antioxidant drugs for neonatal brain injury

The brain injury concept covers a lot of heterogeneity in terms of aetiology involving multiple factors, genetic, hemodynamic, metabolic, nutritional, endocrinological, toxic, and infectious mechanisms, acting in antenatal or postnatal period. Increased vulnerability of the immature brain to oxidative stress is documented because of the limited capacity of antioxidant enzymes and the high free radicals (FRs) generation in rapidly growing tissue. FRs impair transmembrane enzyme Na(+)/K(+)-ATPase activity resulting in persistent membrane depolarization and excessive release of FR and excitatory aminoacid glutamate. Besides being neurotoxic, glutamate is also toxic to oligodendroglia, via FR effects. Neuronal cells die of oxidative stress. Excess of free iron and deficient iron/binding metabolising capacity are additional features favouring oxidative stress in newborn. Each step in the oxidative injury cascade has become a potential target for neuroprotective intervention. The administration of antioxidants for suspected or proven brain injury is still not accepted for clinical use due to uncertain beneficial effects when treatments are started after resuscitation of an asphyxiated newborn. The challenge for the future is the early identification of high-risk babies to target a safe and not toxic antioxidant therapy in combination with standard therapies to prevent brain injury and long-term neurodevelopmental impairment

Increased F2-isoprostane levels in semen and immunolocalization of the 8-iso prostaglandin F2α in spermatozoa from infertile patients with varicocele

Polyunsaturated fatty acid damages lead to alterations in sperm function. This study aimed to investigate the involvement of F2-isoprostanes (F2-IsoPs), oxidized lipid products from arachidonic acid, in sperm quality impairment. For this purpose, F2-IsoP levels in semen and F2-IsoP localization in spermatozoa were explored in infertile subjects affected by idiopathic infertility or varicocele, as well as in fertile men. As compared to fertile men, in the idiopathic infertility and varicocele groups, sperm concentration, motility, morphology, viability, and fertility index were significantly lower and the mean scores concerning sperm apoptosis, necrosis, and immaturity were significantly higher. The idiopathic infertile group showed a reduction in sperm motility and fertility index, as well as an increase of apoptosis and necrosis percentages, in comparison to the varicocele group. The varicocele group showed the highest levels of F2-IsoPs, a significant increase of sperm immaturity, and a significant correlation between F2-IsoP levels and sperm immaturity. 8-Iso Prostaglandin F2α, biomarker of in vivo F2-IsoP, was clearly localized in sperm midpiece and cytoplasmic residues. Data show that F2-IsoP formation is relevant in semen and sperm from infertile patients with varicocele and high percentage of immaturity, suggesting that a correct fatty acid integrity is needed for sperm maturation

Oxidative Stress Biomarkers: Establishment of Reference Values for Isoprostanes, AOPP, and NPBI in Cord Blood

Oxidative stress (OS) is a common pathogenic factor involved in the onset of several diseases in humans, from immunologic disorders to malignancy, being a serious public health problem. In perinatal period, OS has been associated with adverse outcome of pregnancy and neonatal diseases. Dangerous effects of OS are mediated by increased production of free radicals (FRs) following various mechanisms, such as hypoxia, ischemia reperfusion, hyperoxia, inflammation, mitochondrial dysfunction, Fenton chemistry, and prostaglandin metabolism. FRs have short half-life, and their measurement in vivo is faced with many challenges. However, oxyradical derivatives are stable and thus may be measured and monitored repeatedly. The quantification of OS is based on the measurement of specific biomarkers in biologic fluids and tissues, which reflect induced oxidative damage to lipids, proteins, and DNA. Prostanoids, non-protein-bound iron (NPBI), and advanced oxidation protein products (AOPP) are actually considered truly specific and reliable for neonatal injury. Defining reference values for these biomarkers is necessary to investigate their role in neonatal diseases or also to evaluate the success of treatments. In this work, we wanted to define laboratory reference values for biomarkers of OS in a healthy population of term 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

Oxidative Stress in Cancer-Prone Genetic Diseases in Pediatric Age: The Role of Mitochondrial Dysfunction

Oxidative stress is a distinctive sign in several genetic disorders characterized by cancer predisposition, such as Ataxia-Telangiectasia, Fanconi Anemia, Down syndrome, progeroid syndromes, Beckwith-Wiedemann syndrome, and Costello syndrome. Recent literature unveiled new molecular mechanisms linking oxidative stress to the pathogenesis of these conditions, with particular regard to mitochondrial dysfunction. Since mitochondria are one of the major sites of ROS production as well as one of the major targets of their action, this dysfunction is thought to be the cause of the prooxidant status. Deeper insight of the pathogenesis of the syndromes raises the possibility to identify new possible therapeutic targets. In particular, the use of mitochondrial-targeted agents seems to be an appropriate clinical strategy in order to improve the quality of life and the life span of the patients

Rooming-in Reduces Salivary Cortisol Level of Newborn

Background. Rooming-in practice improves breastfeeding and reduces newborn stress reactivity. When this modality is not available, partial rooming-in after birth can be considered. Salivary cortisol levels (SCLs) are considered reliable biomarkers to indicate stress. Objective. To test the hypothesis that rooming-in duration impacts neonatal stress response in hospitalized newborns. Design/methods. Forty term newborns, enrolled in the Neonatology and Obstetrics Nursing, C.G. Ruesch, Naples, Italy, were divided, according to the mother's choice, into the study (SG; n = 20) and control (CG; n = 20) groups if they received full (24 hs) or partial (14 hs) rooming-in care, respectively. Saliva samples were collected from all babies between 7: 00 a.m. and 8: 00 a.m. of the 3rd day of life by using oral swab. Salivary cortisol levels were measured using an enzyme immunoassay kit (Salimetrics LLC, PA, USA). Results. A statistically significant difference in the SCLs between SG and CG was found (median: 258 ng/dl versus 488.5 ng/dl; p = 0 048). Conclusions. Data support the practice of full rooming-in care compared with partial rooming-in. The rooming-in duration clearly reduces SCLs and likely neonatal stress. These lower SCLs may have long-term positive effects reducing the risk of metabolic syndrome, high blood pressure, and cognitive and behavioural changes

Isoprostanes as Biomarker for Patent Ductus Arteriosus in Preterm Infants

Context: It has been reported that isoprostanes (IPs) have a role in the pathophysiology of ductus arteriosus during the fetal and neonatal period. Our aim in this study was to assess if urinary IPs (uIPs) levels correlate with the risk of developing a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. Materials and methods: Infants with 23 + 0 - 33 + 6 weeks of gestational age and respiratory distress syndrome (RDS) were consecutively enrolled. Urine samples were collected on the 2nd and 10th day of life (DOL) for uIPs measurement. Echocardiography for hsPDA diagnosis was performed between 24 and 48 h of life. Regression analysis was performed to assess the correlation between uIPs and hsPDA. Receiver operating characteristic (ROC) curve analysis was used to evaluate the accuracy of the uIPs in predicting the occurrence of hsPDA. Results: Sixty patients were studied: 33 (55%) developed a hsPDA, 27 (45%) had ibuprofen hsPDA closure, and six (10%) required surgical closure. uIPs levels decreased from the 2nd to the 10th DOL. Adjusted regression analysis demonstrated that uIPs on the 2nd DOL were associated (p = 0.02) with the risk of developing a hsPDA. A cut-off level of 1627 ng/mg of creatinine of uIPs predicted the development of a hsPDA with a sensitivity of 82% and a specificity of 73%. Conclusion: Early measurement of uIPs on the 2nd DOL is a reliable biomarker of hsPDA development and, alone or combined with other markers, might represent a non-invasive tool useful for planning the management of PDA in preterm infants

C reactive protein in healthy term newborns during the first 48 hours of life

Background Early-onset neonatal sepsis (EOS) is a serious and potentially life-threatening disease in newborns. C reactive protein (CRP) is the most used laboratory biomarker for the detection of EOS. Little is known about normal reference values of CRP during the perinatal period as several factors are able to influence it. Objectives To identify an appropriate range of CRP values in healthy term newborns during the first 48 hours of life. Design CRP determination was performed in 859 term newborns at 12, 24 and 48 hours of life. Mode of delivery, maternal vaginal culture results, intrapartum antimicrobial prophylaxis (IAP) and other perinatal variables were recorded. Results CRP mean values were significantly higher at 48 hours (4.10 mg/L) than at both 24 (2.30 mg/L) and 12 hours of life (0.80 mg/L). CRP levels were affected by a number of perinatal proinflammatory variables. In particular, CRP mean values were significantly higher in babies born by vaginal delivery (3.80 mg/L) and emergency caesarean section (3.60 mg/L) than in babies born by elective caesarean section (2.10 mg/L). Completed course of IAP led to lower CRP mean values (2.90 mg/L) than IAP not completed (3.80 mg/L) or not performed (4.70 mg/L). Conclusions Postnatal age and mode of delivery significantly influence CRP values. Reliable reference values are crucial in order to obtain an adequate diagnostic accuracy