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      Effects of vitamin B-6 supplementation on oxidative stress and inflammatory response in neonatal rats receiving hyperoxia therapy

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          Abstract

          Hyperoxia is often used in the treatment of neonates. However, protracted use of hyper-oxia leads to significant morbidity. The purpose of this study was to evaluate the effects of vitamin B-6 supplementation on oxidative stress and inflammatory responses in neonatal rats undergoing hyperoxia therapy. The study consisted of 2 parts: a survival study and a vitamin B-6 efficacy study for 16 days. Neonatal rats were randomly divided into either the control group, B-6 group (subcutaneously injected with 90 mg/kg/d of pyridoxal 5′-phosphate [PLP]), O 2 group (treated with 85% oxygen), or O 2 + B-6 group (simultaneously treated with 85% oxygen and 90 mg/kg/d PLP). After the survival study was done, the vitamin B-6 efficacy study was performed with duplicate neonatal rats sacrificed on the 3rd, 6th, 9th, and 16th day. Serum inflammatory cytokines, tissue pathology, and malondialdehyde (MDA) levels were measured. In the survival study, the survival rate of neonatal rats in the control, B-6, O 2, and O 2 + B-6 group on the 16th day were 100%, 100%, 25%, and 62.50%, respectively. The efficacy study showed lung polymorphonuclear granulocyte (PMN) and macrophage infiltration, increased liver hemopoiesis, and higher MDA levels in liver homogenates at days 3 through 16 in the O 2 group. Vitamin B-6 supplementation considerably increased serum inflammatory cytokines in either the 6th or 9th day and decreased liver MDA level before the 6th day. These results indicate that neonatal rats receiving hyperoxia treatment suffered divergent serum inflammatory responses and were in increased liver oxidative stress. Vitamin B-6 supplementation seemed to improve survival rates, change systemic inflammatory response, and decrease liver oxidative stress while neonatal rats were under hyperoxia treatment.

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          Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia.

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            Functional and pathological effects of prolonged hyperoxia in neonatal mice.

            Bronchopulmonary dysplasia (BPD) commonly develops in premature infants. An improved understanding of the pathophysiology of BPD requires better models. In this study, neonatal FVB/N mice were exposed to room air or 85% oxygen for 28 days. Neonatal hyperoxia resulted in decreased alveolar septation, increased terminal air space size, and increased lung fibrosis. These changes were evident after 7 days and more pronounced by 28 days. Decreased alveolarization was preceded by decreased proliferation of lung cells. After 3 days of hyperoxia, cell proliferation was decreased compared with room air littermates. Cell proliferation continued to be decreased in the first 2 wk but normalized by 4 wk. Hyperoxia caused an increased number of inflammatory cells in lung tissue and in lung lavage fluid. Analysis of lung tissue RNA by RT-PCR showed that hyperoxia increased expression of the proinflammatory cytokines interleukin-1alpha and macrophage inflammatory protein-1alpha. Prolonged neonatal hyperoxia caused functional changes, decreasing lung volume and pulmonary compliance. We conclude that prolonged exposure of neonatal mice to hyperoxia creates a lesion that is very similar to human BPD and suggests that altered cell proliferation may be important in the pathogenesis of chronic neonatal lung disease.
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              Consequences of Hyperoxia and the Toxicity of Oxygen in the Lung

              Oxygen (O2) is life essential but as a drug has a maximum positive biological benefit and accompanying toxicity effects. Oxygen is therapeutic for treatment of hypoxemia and hypoxia associated with many pathological processes. Pathophysiological processes are associated with increased levels of hyperoxia-induced reactive O2 species (ROS) which may readily react with surrounding biological tissues, damaging lipids, proteins, and nucleic acids. Protective antioxidant defenses can become overwhelmed with ROS leading to oxidative stress. Activated alveolar capillary endothelium is characterized by increased adhesiveness causing accumulation of cell populations such as neutrophils, which are a source of ROS. Increased levels of ROS cause hyperpermeability, coagulopathy, and collagen deposition as well as other irreversible changes occurring within the alveolar space. In hyperoxia, multiple signaling pathways determine the pulmonary cellular response: apoptosis, necrosis, or repair. Understanding the effects of O2 administration is important to prevent inadvertent alveolar damage caused by hyperoxia in patients requiring supplemental oxygenation.
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                Author and article information

                Journal
                J Food Drug Anal
                J Food Drug Anal
                Journal of Food and Drug Analysis
                Taiwan Food and Drug Administration
                1021-9498
                2224-6614
                2018
                02 February 2018
                : 26
                : 3
                : 1086-1096
                Affiliations
                [a ]Department of Pediatric Pulmonology and Critical Care, Changhua Christian Children Hospital, Changhua, Taiwan
                [b ]Graduate Program in Nutrition, Chung Shan Medical University, Taichung, Taiwan
                [c ]Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
                [d ]Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan
                [e ]Department of Pediatric Neurology, Changhua Christian Children Hospital, Changhua, Taiwan
                [f ]Department of Pediatric Immunology, Changhua Christian Children Hospital, Changhua, Taiwan
                [g ]Department of Neonatal Medicine, Changhua Christian Children Hospital, Changhua, Taiwan
                [h ]Department of Pediatric Gastrointestinology and Hepatology, Changhua Christian Children Hospital, Changhua, Taiwan
                [i ]Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua, Taiwan
                [j ]Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan
                Author notes
                [* ]Corresponding author. Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan. Fax: +886 4 23248175. E-mail address: clhsu@ 123456csmu.edu.tw (C.-L. Hsu).
                Article
                jfda-26-03-1086
                10.1016/j.jfda.2018.01.004
                9303020
                29976401
                488a0048-4418-481f-86f6-c0c0ea06aa24
                © 2018 Taiwan Food and Drug Administration

                This is an open access article under the CC-BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 25 October 2017
                : 08 January 2018
                : 10 January 2018
                Funding
                Funded by: The Changhua Christian Hospital
                Award ID: 105-CCH-IRP-034
                The Changhua Christian Hospital provided funding for the experiment. The project number was 105-CCH-IRP-034.
                Categories
                Original Article

                hyperoxia,inflammation,neonate,oxidative stress,vitamin b-6
                hyperoxia, inflammation, neonate, oxidative stress, vitamin b-6

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