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1.
Neonatology ; 112(1): 1-8, 2017.
Article in English | MEDLINE | ID: mdl-28142140

ABSTRACT

BACKGROUND: Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurological morbidity in infants and children. Oxidative stress due to free radical formation and the initiation of abnormal oxidative reactions appears to play a key role. Docosahexanoic acid (DHA), a main component of brain membrane phospholipids, may act as a neuroprotectant after hypoxia-ischemia by regulating multiple molecular pathways and gene expression. OBJECTIVES: The aims of this study were to test the hypothesis that DHA provides significant protection against lipoperoxidation damage in the cerebral cortex and hippocampus in a neonatal piglet model of severe hypoxia-reoxygenation. METHODS: Newborn piglets, Noroc (LYLD), were subjected to severe global hypoxia. One group was resuscitated with ambient air (21% group, n = 11) and another also received 5 mg/kg of DHA 4 h after the end of hypoxia (21% DHA group, n = 10). After 9.5 h, tissues from the prefrontal cortex and hippocampus were sampled and the levels of isoprostanes, neuroprostanes, neurofurans, and F2-dihomo-isoprostanes were determined by the liquid chromatography triple quadrupole mass spectrometry technique. RESULTS: Lipid peroxidation biomarkers were significantly lower in both the cortex and hippocampus in the DHA-treated group compared with the untreated group. CONCLUSIONS: The present study demonstrates that DHA administration after severe hypoxia in newborn piglets has an antioxidative effect in the brain, suggesting a protective potential of DHA if given after injuries to the brain.


Subject(s)
Antioxidants/pharmacology , Asphyxia Neonatorum/drug therapy , Docosahexaenoic Acids/pharmacology , Hippocampus/drug effects , Hypoxia-Ischemia, Brain/drug therapy , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Prefrontal Cortex/drug effects , Animals , Animals, Newborn , Asphyxia Neonatorum/metabolism , Asphyxia Neonatorum/pathology , Biomarkers/metabolism , Disease Models, Animal , Furans/metabolism , Hippocampus/metabolism , Hippocampus/pathology , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/pathology , Isoprostanes/metabolism , Lipid Peroxidation/drug effects , Neuroprostanes/metabolism , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , Sus scrofa
2.
Tumori ; 100(6): 590-9, 2014.
Article in English | MEDLINE | ID: mdl-25688491

ABSTRACT

Oxidative stress plays a key role in carcinogenesis. Oxidative damage to cell components can lead to the initiation, promotion and progression of cancer. Oxidative stress is also a distinctive sign in several genetic disorders characterized by a cancer predisposition such as ataxia-telangiectasia, Fanconi anemia, Down syndrome, Beckwith-Wiedemann syndrome and Costello syndrome. Taking into account the link between oxidative stress and cancer, the capacity of antioxidant agents to prevent or delay neoplastic development has been tested in various studies, both in vitro and in vivo, with interesting and promising results. In recent years, research has been conducted into the molecular mechanisms linking oxidative stress to the pathogenesis of the genetic syndromes we consider in this review, with the resulting identification of possible new therapeutic targets. The aim of this review is to focus on the oxidative mechanisms intervening in carcinogenesis in cancer-prone genetic disorders and to analyze the current status and future prospects of antioxidants.


Subject(s)
Antioxidants/therapeutic use , Genetic Diseases, Inborn/complications , Genetic Diseases, Inborn/metabolism , Neoplasms/metabolism , Neoplasms/prevention & control , Oxidative Stress , Ataxia Telangiectasia/complications , Ataxia Telangiectasia/metabolism , Beckwith-Wiedemann Syndrome/complications , Beckwith-Wiedemann Syndrome/metabolism , Carcinogenesis/genetics , Carcinogenesis/metabolism , Costello Syndrome/complications , Costello Syndrome/metabolism , Down Syndrome/complications , Down Syndrome/metabolism , Fanconi Anemia/complications , Fanconi Anemia/metabolism , Humans , Infant , Neoplasms/genetics , Oxidative Stress/drug effects , Risk
3.
Anticancer Res ; 33(2): 691-5, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23393369

ABSTRACT

BACKGROUND: Costello syndrome is a rare genetic condition characterized by coarse facies, short stature, loose folds of skin especially on hands and feet, severe feeding difficulties and failure to thrive. Other features include cardiac anomalies, developmental disability and increased risk of neoplasms. Given the link between oxidative stress (OS) and carcinogenesis, we tested the hypothesis that OS occurs in this syndrome, supposing its role both in cancer development and in other clinical features. PATIENTS AND METHODS: We describe four cases with Costello syndrome in which we verified the presence of OS by measuring a redox biomarker profile including total hydroperoxides, non-protein-bound iron, advanced oxidation protein products, thyols, carbonyl groups and isoprostanes. Thus, we introduced an antioxidant agent, namely potassium ascorbate with ribose (PAR) into the therapy and monitored the redox profile every three months to verify its efficacy. RESULTS: A progressive decrease in OS biomarkers occurred, together with an improvement in the clinical features of the patients. CONCLUSION: OS was proven in all four cases of Costello syndrome. The antioxidant therapy with PAR demonstrated positive effects. These promising results need further research to confirm the relevance of OS and the efficacy of PAR therapy in Costello syndrome.


Subject(s)
Antioxidants/therapeutic use , Ascorbic Acid/therapeutic use , Costello Syndrome/drug therapy , Costello Syndrome/physiopathology , Oxidative Stress , Costello Syndrome/metabolism , Female , Humans , Infant, Newborn , Male , Oxidation-Reduction , Ribose/therapeutic use
4.
Front Biosci (Elite Ed) ; 2(4): 1514-9, 2010 06 01.
Article in English | MEDLINE | ID: mdl-20515822

ABSTRACT

The aim of the No Pain in Labour (NoPiL) study was to evaluate the stress and clinical outcome of infants vaginally born without maternal analgesia and after maternal epidural or systemic analgesia. We studied 120 healthy term infants, 41 in the no analgesia group, 38 in the epidural analgesia group, and 41 in the systemic analgesia group. Cortisol, beta-endorphin, oxidative stress markers (ie: total hydroperoxide (TH) and advanced oxidation protein products (AOPP)), interleukin-1beta (IL-1beta), and interleukin-8 (IL-8) cytokines were measured in arterial cord blood samples. Infants in the 3 groups had similar Apgar score, cord blood pH and occurrence of hypoglycaemia, hyperbilirubinemia, and respiratory depression. Cortisol and endorphin plasma levels did not differ in the groups, nor did TH and AOPP values. IL-1beta and IL-8 cytokine were higher in infants born after maternal epidural analgesia than in other groups. Short-term outcome and stress were similar in infants vaginally born without maternal analgesia and after epidural and systemic analgesia. The possible implications of the highest interleukin levels in the epidural analgesia group deserve further study.


Subject(s)
Analgesia, Epidural , Analgesics/administration & dosage , Maternal Exposure , Female , Humans , Hydrocortisone/blood , Infant, Newborn , Interleukin-1/blood , Interleukin-8/blood , Oxidative Stress , Pregnancy , beta-Endorphin/blood
5.
Pediatr Pulmonol ; 44(11): 1125-31, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19830697

ABSTRACT

Despite the role of reactive oxygen species in the development of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants, the anti-oxidant properties of commercial surfactants have never been studied. We measured the superoxide dismutase (SOD) and catalase (CAT) activity, the scavenger activity against hydrogen peroxide (H(2)O(2)), and its changes after the addition of SOD and CAT in four natural surfactants, namely Infasurf, Curosurf, Survanta, and Alveofact. We found that they contain measurable amount of SOD and CAT. Curosurf and Survanta seem to have higher antioxidant effect than Infasurf and Alveofact. Moreover, the highest phospholipid concentration and recommended dose of Curosurf imply that its scavenger activity for each treatment dose in preterm infants is likely higher than that of Survanta. Finally, the supplementation with SOD and CAT induced a remarkable increase of antioxidant action in all studied surfactants.


Subject(s)
Catalase/analysis , Pulmonary Surfactants/chemistry , Superoxide Dismutase/analysis , Biological Products/chemistry , Free Radical Scavengers/analysis , Humans , Hydrogen Peroxide/analysis , Phospholipids/chemistry
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