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Effect of postnatal malnutrition on hyperoxia-induced newborn lung development

MATALOUN, M.M.G.B.; LEONE, C.R.; MASCARETTI, R.S.; DOHLNIKOFF, M.; REBELLO, C.M.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
37.43%
Several factors are associated with bronchopulmonary dysplasia. Among them, hyperoxia and lung immaturity are considered to be fundamental; however, the effect of malnutrition is unknown. Our objective was to evaluate the effects of 7 days of postnatal malnutrition and hyperoxia on lung weight, volume, water content, and pulmonary morphometry of premature rabbits. After c-section, 28-day-old New Zealand white rabbits were randomized into four groups: control diet and room air (CA, N = 17), control diet and ≥95% O2 (CH, N = 17), malnutrition and room air (MA, N = 18), and malnutrition and ≥95% O2 (MH, N = 18). Malnutrition was defined as a 30% reduction of all the nutrients provided in the control diet. Treatments were maintained for 7 days, after which histological and morphometric analyses were conducted. Lung slices were stained with hematoxylin-eosin, modified orcein-resorcin or picrosirius. The results of morphometric analysis indicated that postnatal malnutrition decreased lung weight (CA: 0.83 ± 0.19; CH: 0.96 ± 0.28; MA: 0.65 ± 0.17; MH: 0.79 ± 0.22 g) and water content, as well as the number of alveoli (CA: 12.43 ± 3.07; CH: 8.85 ± 1.46; MA: 7.33 ± 0.88; MH: 6.36 ± 1.53 x 10-3/mm) and elastic and collagen fibers. Hyperoxia reduced the number of alveoli and increased septal thickening and the mean linear intercept. The reduction of alveolar number...

Blood gases and cardiovascular shunt in the South American lungfish (Lepidosiren paradoxa) during normoxia and hyperoxia

BASSI, Mirian; GIUSTI, Humberto; SILVA, Glauber S. da; AMIN-NAVES, Jalile; GLASS, Mogens L.
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
37.37%
The South American lungfish (Lepidosiren paradoxa) has an arterial P(O2), (Pa(O2)) as high as 70-100 mm Hg, corresponding to Hb-O(2) saturations from 90% to 95%, which indicates a moderate cardiovascular right to left (R-L) shunt. In hyperoxia (50% O(2)), we studied animals in: (1) aerated water combined with aerial hyperoxia, which increased Pa(O2) from 78 +/- 2 to 114 +/- 3 mm Hg and (2) and aquatic hyperoxia (50% O(2)) combined room air, which gradually increased Pa(O2) from 75 +/- 4 mm Hg to as much as 146 +/- 10 mm Hg. Further, the hyperoxia (50%) depressed pulmonary ventilation from 58 +/- 13 to 5.5 +/- 3.0 mLBTPS kg h(-1), and Pa(CO2) increased from 20 +/- 2 to 31 +/- 4 mm Hg, while pHa became reduced from 7.56 +/- 0.03 to 7.31 +/- 0.09. At the same time, venous P(O2) (Pv(O2)) rose from 40.0 +/- 2.3 to 46.4 +/- 1.2 mm Hg and, concomitantly, Pvco, increased from 23.2 +/- 1.1 to 32.2 +/- 0.5 mm Hg. R-L shunts were estimated to about 19%, which is moderate when compared to most amphibians. (C) 2010 Elsevier B.V. All rights reserved.; FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)[Proc 98/06731-5]; CNPq (Conselho Nacional de Desen-volvimento Cientifico o Tecnologico)[Proc. 520769/93-7]; FAEPA (Fundacao de Apoio ao Ensino...

Effect of postnatal malnutrition on hyperoxia-induced newborn lung development

Mataloun,M.M.G.B.; Leone,C.R.; Mascaretti,R.S.; Dohlnikoff,M.; Rebello,C.M.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2009 Português
Relevância na Pesquisa
37.43%
Several factors are associated with bronchopulmonary dysplasia. Among them, hyperoxia and lung immaturity are considered to be fundamental; however, the effect of malnutrition is unknown. Our objective was to evaluate the effects of 7 days of postnatal malnutrition and hyperoxia on lung weight, volume, water content, and pulmonary morphometry of premature rabbits. After c-section, 28-day-old New Zealand white rabbits were randomized into four groups: control diet and room air (CA, N = 17), control diet and ≥95% O2 (CH, N = 17), malnutrition and room air (MA, N = 18), and malnutrition and ≥95% O2 (MH, N = 18). Malnutrition was defined as a 30% reduction of all the nutrients provided in the control diet. Treatments were maintained for 7 days, after which histological and morphometric analyses were conducted. Lung slices were stained with hematoxylin-eosin, modified orcein-resorcin or picrosirius. The results of morphometric analysis indicated that postnatal malnutrition decreased lung weight (CA: 0.83 ± 0.19; CH: 0.96 ± 0.28; MA: 0.65 ± 0.17; MH: 0.79 ± 0.22 g) and water content, as well as the number of alveoli (CA: 12.43 ± 3.07; CH: 8.85 ± 1.46; MA: 7.33 ± 0.88; MH: 6.36 ± 1.53 x 10-3/mm) and elastic and collagen fibers. Hyperoxia reduced the number of alveoli and increased septal thickening and the mean linear intercept. The reduction of alveolar number...

Effect of hyperoxia on the intestinal IgA secretory component in neonatal rats and on intestinal epithelial cells in vitro

Li,J.J.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2010 Português
Relevância na Pesquisa
37.37%
Oxygen therapy is essential for the treatment of some neonatal critical care conditions but its extrapulmonary effects have not been adequately investigated. We therefore studied the effects of various oxygen concentrations on intestinal epithelial cell function. In order to assess the effects of hyperoxia on the intestinal immunological barrier, we studied two physiological changes in neonatal rats exposed to hyperoxia: the change in intestinal IgA secretory component (SC, an important component of SIgA) and changes in intestinal epithelial cells. Immunohistochemistry and Western blot were used to detect changes in the intestinal tissue SC of neonatal rats. To detect intestinal epithelial cell growth, cells were counted, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Giemsa staining were used to assess cell survival. Immunohistochemistry was used to determine SC expression. The expression of intestinal SC in neonatal rats under hyperoxic conditions was notably increased compared with rats inhaling room air (P < 0.01). In vitro, 40% O2 was beneficial for cell growth. However, 60% O2 and 90% O2 induced rapid cell death. Also, 40% O2 induced expression of SC by intestinal epithelial cells, whereas 60% O2did not; however...

Hyperoxia and the antimicrobial susceptibility of Escherichia coli and Pseudomonas aeruginosa.

Muhvich, K H; Park, M K; Myers, R A; Marzella, L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1989 Português
Relevância na Pesquisa
27.59%
We have tested the ability of hyperoxia (98% O2-2% CO2 at 2.8 atmospheres absolute [ca. 284.6 kPa]) to enhance killing of Escherichia coli (serotype O18 or ATCC 25922) by nitrofurantoin, sulfamethoxazole, trimethoprim, gentamicin, and tobramycin. We have also looked for interactions between hyperoxia and the aminoglycosides against Pseudomonas aeruginosa ATCC 27853. Hyperoxia significantly enhanced bacteriostatic activity of nitrofurantoin and trimethoprim as measured by MIC testing. The possibility exists that these effects might be due to the method required to tests MICs under hyperoxic conditions rather than to the effect of hyperoxia itself. In addition, hyperoxia enhanced killing of bacteria by trimethoprim as measured by MBC testing. Hyperoxia decreased numbers of E. coli by 1.3 log10 and P. aeruginosa by 2.7 log10 in cation-supplemented Mueller-Hinton broth medium. The bacteriostatic effects of hyperoxia did not affect MICs of gentamicin or tobramycin. The lack of interaction between hyperoxia and gentamicin or tobramycin was confirmed by determining the number of viable bacteria remaining after 24 h of exposure to hyperoxia by using a pour plate method. We conclude that hyperoxia potentiates the antimicrobial activity of the reduction-oxidation-cycling antibiotic tested (nitrofurantoin) and of one of the antimetabolites tested (trimethoprim). Hyperoxia does not enhance the bactericidal effects of gentamicin and tobramycin...

Cellular factors required for protection from hyperoxia toxicity in Saccharomyces cerevisiae

Outten, Caryn E.; Falk, Robert L.; Culotta, Valeria C.
Fonte: Portland Press Ltd. Publicador: Portland Press Ltd.
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.57%
Prolonged exposure to hyperoxia represents a serious danger to cells, yet little is known about the specific cellular factors that affect hyperoxia stress. By screening the yeast deletion library, we have identified genes that protect against high-O2 damage. Out of approx. 4800 mutants, 84 were identified as hyperoxia-sensitive, representing genes with diverse cellular functions, including transcription and translation, vacuole function, NADPH production, and superoxide detoxification. Superoxide plays a significant role, since the majority of hyperoxia-sensitive mutants displayed cross-sensitivity to superoxide-generating agents, and mutants with compromised SOD (superoxide dismutase) activity were particularly vulnerable to hyperoxia. By comparison, factors known to guard against H2O2 toxicity were poorly represented amongst hyperoxia-sensitive mutants. Although many cellular components are potential targets, our studies indicate that mitochondrial glutathione is particularly vulnerable to hyperoxia damage. During hyperoxia stress, mitochondrial glutathione is more susceptible to oxidation than cytosolic glutathione. Furthermore, two factors that help maintain mitochondrial GSH in the reduced form, namely the NADH kinase Pos5p and the mitochondrial glutathione reductase (Glr1p)...

Induced recovery of hypoxic phrenic responses in adult rats exposed to hyperoxia for the first month of life

Fuller, D D; Wang, Z-Y; Ling, L; Olson, E B; Bisgard, G E; Mitchell, G S
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em 01/11/2001 Português
Relevância na Pesquisa
27.59%
Adult rats exposed to hyperoxia for the first month of life have permanently attenuated ventilatory and phrenic nerve responses to hypoxia. We tested the hypothesis that the blunted hypoxic phrenic response in hyperoxia-treated rats (inspired O2 fraction, FI,O2 = 0.6 for 28 post-natal days) could be actively restored to normal by intermittent (alternating 12 % O2/air at 5 min intervals; 12 h per night for 1 week) or sustained (12 % O2 for 1 week) hypoxia.Phrenic responses to isocapnic hypoxia(Pa,O2 = 60, 50 and 40 ± 2 mmHg) were assessed in the following groups of anaesthetized, vagotomized adult Sprague-Dawley rats (age 4 months), treated with a neuromuscular blocking agent and ventilated: control, hyperoxia-treated and hyperoxia-treated exposed to either intermittent or sustained hypoxia as adults. Experiments on intermittent and sustained hypoxia-treated rats were performed on the morning following hypoxic exposures.Both intermittent and sustained hypoxia enhanced hypoxic phrenic responses in hyperoxia-treated rats when expressed as minute phrenic activity (P < 0.05). Increases in phrenic burst amplitude during hypoxia were greater in hyperoxia-treated rats after intermittent hypoxia (P < 0.05), and a similar but non-significant trend was observed after sustained hypoxia. Hypoxia-induced changes in phrenic burst frequency were not significantly different among groups.The estimated carotid body volume in control rats (11.5 (± 0.7) × 106μm3) was greater than in the other treatment groups (P < 0.05). However...

Life-long impairment of hypoxic phrenic responses in rats following 1 month of developmental hyperoxia

Fuller, D D; Bavis, R W; Vidruk, E H; Wang, Z-Y; Olson, E B; Bisgard, G E; Mitchell, G S
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em 01/02/2002 Português
Relevância na Pesquisa
27.57%
Hypoxic ventilatory and phrenic responses are reduced in adult rats (3–5 months old) exposed to hyperoxia for the first month of life (hyperoxia treated). We previously reported that hypoxic phrenic responses were normal in a small sample of 14- to 15-month-old hyperoxia-treated rats, suggesting slow, spontaneous recovery. Subsequent attempts to identify the mechanism(s) underlying this spontaneous recovery of hypoxic phrenic responses led us to re-evaluate our earlier conclusion. Experiments were conducted in two groups of aged Sprague-Dawley rats (14–15 months old) which were anaesthetized, vagotomized, neuromuscularly blocked and ventilated: (1) a hyperoxia-treated group raised in 60 % O2 for the first 28 postnatal days; and (2) an age-matched control group raised in normoxia. Increases in minute phrenic activity and integrated phrenic nerve amplitude (∫Phr) during isocapnic hypoxia (arterial partial pressures of O2, 60, 50 and 40 ± 1 mmHg) were greater in aged control (n = 15) than hyperoxia-treated rats (n = 11; P≤ 0.01). Phrenic burst frequency during hypoxia was not different between groups. To examine the central integration of carotid chemoafferent inputs, steady-state relationships between carotid sinus nerve (electrical) stimulation frequency and phrenic nerve activity were compared in aged control (n = 7) and hyperoxia-treated rats (n = 7). Minute phrenic activity...

Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS

Klimova, Tatyana A.; Bell, Eric L.; Shroff, Emelyn H.; Weinberg, Frank D.; Snyder, Colleen M.; Dimri, Goberdan P.; Schumacker, Paul T.; Budinger, G. R. Scott; Chandel, Navdeep S.
Fonte: The Federation of American Societies for Experimental Biology Publicador: The Federation of American Societies for Experimental Biology
Tipo: Artigo de Revista Científica
Publicado em /03/2009 Português
Relevância na Pesquisa
27.57%
Senescence is a potential tumor-suppressing mechanism and a commonly used model of cellular aging. One current hypothesis to explain senescence, based in part on the correlation of oxygen with senescence, postulates that it is caused by oxidative damage from reactive oxygen species (ROS). Here, we further test this theory by determining the mechanisms of hyperoxia-induced senescence. Exposure to 70% O2 led to stress-induced, telomere-independent senescence. Although hyperoxia elevated mitochondrial ROS production, overexpression of antioxidant proteins was not sufficient to prevent hyperoxia-induced senescence. Hyperoxia activated AMPK; however, overexpression of a kinase-dead mutant of LKB1, which prevented AMPK activation, did not prevent hyperoxia-induced senescence. Knocking down p21 via shRNA, or suppression of the p16/pRb pathway by either BMI1 or HPV16-E7 overexpression, was also insufficient to prevent hyperoxia-induced senescence. However, suppressing p53 function resulted in partial rescue from senescence, suggesting that hyperoxia-induced senescence involves p53. Suppressing both the p53 and pRb pathways resulted in almost complete protection, indicating that both pathways cooperate in hyperoxia-induced senescence. Collectively...

Deletion of caveolin-1 protects hyperoxia-induced apoptosis via survivin-mediated pathways

Zhang, Meng; Lin, Ling; Lee, Seon-Jin; Mo, Li; Cao, Jiaofei; Ifedigbo, Emeka; Jin, Yang
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.57%
Hyperoxia-induced lung injury is an established model that mimics human acute respiratory distress syndrome. Cell death is a prominent feature in lungs following prolonged hyperoxia. Caveolae are omega-shaped invaginations of the plasma membrane. Caveolin-1 (cav-1), a 22-kDa transmembrane scaffolding protein, is the principal structural component of caveolae. We have recently shown that deletion of cav-1 (cav-1−/−) protected against hyperoxia-induced cell death and lung injury both in vitro and in vivo; however, the mechanisms remain unclear. Survivin, a member of the inhibitor of apoptosis protein family, inhibits apoptosis in tumor cells. Although emerging evidence suggests that survivin is involved in wound healing, especially in vascular injuries, its role in hyperoxia-induced lung injury has not been investigated. Our current data demonstrated that hyperoxia induced apoptosis via suppressing survivin expression. Deletion of cav-1 abolished this suppression and subsequently protected against hyperoxia-induced apoptosis. Using “gain” and “loss” of function assays, we determined that survivin protected lung cells from hyperoxia-induced apoptosis via the inhibition of apoptosis executor caspase-3. Overexpression of survivin by deletion of cav-1 was regulated by Egr-1. Egr-1 functioned as a negative regulator of survivin expression. Deletion of cav-1 upregulated survivin via decreased Egr-1 binding of the survivin promoter region. Together...

Hyperoxia disrupts vascular endothelial growth factor-nitric oxide signaling and decreases growth of endothelial colony-forming cells from preterm infants

Fujinaga, Hideshi; Baker, Christopher D.; Ryan, Sharon L.; Markham, Neil E.; Seedorf, Gregory J.; Balasubramaniam, Vivek; Abman, Steven H.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.64%
Exposure of preterm infants to hyperoxia impairs vascular growth, contributing to the development of bronchopulmonary dysplasia and retinopathy of prematurity. Disruption of vascular endothelial growth factor (VEGF)-nitric oxide (NO) signaling impairs vascular growth. Endothelial progenitor cells (EPCs) may play an important role in vascular growth. Endothelial colony-forming cells (ECFCs), a type of EPC, from human preterm cord blood are more susceptible to hyperoxia-induced growth impairment than term ECFCs. Therefore, we hypothesized that hyperoxia disrupts VEGF-NO signaling and impairs growth in preterm ECFCs and that exogenous VEGF or NO preserves growth in hyperoxia. Growth kinetics of preterm cord blood-derived ECFCs (gestational ages, 27–34 wk) were assessed in room air (RA) and hyperoxia (40–50% oxygen) with or without VEGF, NO, or Nω-nitro-l-arginine. VEGF, VEGF receptor-2 (VEGFR-2), and endothelial NO synthase (eNOS) protein expression and NO production were compared. Compared with RA controls, hyperoxia significantly decreased growth, VEGFR-2 and eNOS expression, and NO production. VEGF treatment restored growth in hyperoxia to values measured in RA controls and significantly increased eNOS expression in hyperoxia. NO treatment also increased growth in hyperoxia. Nω-nitro-l-arginine treatment inhibited VEGF-augmented growth in RA and hyperoxia. We conclude that hyperoxia decreases growth and disrupts VEGF-NO signaling in human preterm ECFCs. VEGF treatment restores growth in hyperoxia by increasing NO production. NO treatment also increases growth during hyperoxia. Exogenous VEGF or NO may protect preterm ECFCs from the adverse effects of hyperoxia and preservation of ECFC function may improve outcomes of preterm infants.

Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia

Shin, Hwa Kyoung; Dunn, Andrew K.; Jones, Phillip B.; Boas, David A.; Lo, Eng H.; Moskowitz, Michael A.; Ayata, Cenk
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
27.59%
Normobaric hyperoxia is under investigation as a treatment for acute ischaemic stroke. In experimental models, normobaric hyperoxia reduces cerebral ischaemic injury and improves functional outcome. The mechanisms of neuroprotection are still debated because, (i) inhalation of 100% O2 does not significantly increase total blood O2 content; (ii) it is not known whether normobaric hyperoxia increases O2 delivery to the severely ischaemic cortex because of its short diffusion distance; and (iii) hyperoxia may reduce collateral cerebral blood flow (CBF) to ischaemic penumbra because it can cause vasoconstriction. We addressed these issues using real-time two-dimensional multispectral reflectance imaging and laser speckle flowmetry to simultaneously and non-invasively determine the impact of normobaric hyperoxia on CBF and oxygenation in ischaemic cortex. Ischaemia was induced by distal middle cerebral artery occlusion (dMCAO) in normoxic (30% inhaled O2, arterial pO2 134 ± 9 mmHg), or hyperoxic mice (100% inhaled O2 starting 15 min after dMCAO, arterial pO2 312 ± 10 mmHg). Post-ischaemic normobaric hyperoxia caused an immediate and progressive increase in oxyhaemoglobin (oxyHb) concentration, nearly doubling it in ischaemic core within 60 min. In addition...

PKR-dependent CHOP induction limits hyperoxia-induced lung injury

Lozon, Tricia I.; Eastman, Alison J.; Matute-Bello, Gustavo; Chen, Peter; Hallstrand, Teal S.; Altemeier, William A.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Português
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27.57%
Supplemental O2 is commonly employed in patients with respiratory failure; however, hyperoxia is also a potential contributor to lung injury. In animal models, hyperoxia causes oxidative stress in the lungs, resulting in increased inflammation, edema, and permeability. We hypothesized that oxidative stress from prolonged hyperoxia leads to endoplasmic reticulum (ER) stress, resulting in activation of the unfolded protein response (UPR) and induction of CCAAT enhancer-binding protein homologous protein (CHOP), a transcription factor associated with cell death in the setting of persistent ER stress. To test this hypothesis, we exposed the mouse lung epithelial cell line MLE-12 to 95% O2 for 8–24 h and evaluated for evidence of UPR induction and CHOP induction. Hyperoxia caused increased CHOP expression without other evidence of UPR activation. Because CHOP expression is preceded by phosphorylation of the α-subunit of the eukaryotic initiation factor-2 (eIF2α), we evaluated the role of double-stranded RNA-activated protein kinase (PKR), a non-UPR-associated eIF2α kinase. Hyperoxia caused PKR phosphorylation, and RNA interference knockdown of PKR attenuated hyperoxia-induced CHOP expression. In vivo, hyperoxia induced PKR phosphorylation and CHOP expression in the lungs without other biochemical evidence for ER stress. Additionally...

Hyperoxia-Induced LC3B Interacts with the Fas Apoptotic Pathway in Epithelial Cell Death

Tanaka, Akihiko; Jin, Yang; Lee, Seon-Jin; Zhang, Meng; Kim, Hong Pyo; Stolz, Donna B.; Ryter, Stefan W.; Choi, Augustine M. K.
Fonte: American Thoracic Society Publicador: American Thoracic Society
Tipo: Artigo de Revista Científica
Publicado em /04/2012 Português
Relevância na Pesquisa
27.59%
Epithelial cell death plays a critical role in hyperoxia-induced lung injury. We investigated the involvement of the autophagic marker microtubule-associated protein-1 light chain-3B (LC3B) in epithelial cell apoptosis after hyperoxia. Prolonged hyperoxia (>95% O2), which causes characteristic lung injury in mice, activated morphological and biochemical markers of autophagy. Hyperoxia induced the time-dependent expression and conversion of LC3B-I to LC3B-II in mouse lung in vivo and in cultured epithelial cells (Beas-2B, human bronchial epithelial cells) in vitro. Hyperoxia increased autophagosome formation in Beas-2B cells, as evidenced by electron microscopy and increased GFP-LC3 puncta. The augmented LC3B level after hyperoxia was transcriptionally regulated and dependent in part on the c-Jun N-terminal kinase pathway. We hypothesized that LC3B plays a regulatory role in hyperoxia-induced epithelial apoptosis. LC3B siRNA promoted hyperoxia-induced cell death in epithelial cells, whereas overexpression of LC3B conferred cytoprotection after hyperoxia. The autophagic protein LC3B cross-regulated the Fas apoptotic pathway by physically interacting with the components of death-inducing signaling complex. This interaction was mediated by caveolin-1 tyrosine 14...

Hyperoxia Decreases Glycolytic Capacity, Glycolytic Reserve and Oxidative Phosphorylation in MLE-12 Cells and Inhibits Complex I and II Function, but Not Complex IV in Isolated Mouse Lung Mitochondria

Das, Kumuda C.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 02/09/2013 Português
Relevância na Pesquisa
27.59%
High levels of oxygen (hyperoxia) are frequently used in critical care units and in conditions of respiratory insufficiencies in adults, as well as in infants. However, hyperoxia has been implicated in a number of pulmonary disorders including bronchopulmonary dysplasia (BPD) and adult respiratory distress syndrome (ARDS). Hyperoxia increases the generation of reactive oxygen species (ROS) in the mitochondria that could impair the function of the mitochondrial electron transport chain. We analyzed lung mitochondrial function in hyperoxia using the XF24 analyzer (extracellular flux) and optimized the assay for lung epithelial cells and mitochondria isolated from lungs of mice. Our data show that hyperoxia decreases basal oxygen consumption rate (OCR), spare respiratory capacity, maximal respiration and ATP turnover in MLE-12 cells. There was significant decrease in glycolytic capacity and glycolytic reserve in MLE-12 cells exposed to hyperoxia. Using mitochondria isolated from lungs of mice exposed to hyperoxia or normoxia we have shown that hyperoxia decreased the basal, state 3 and state3 μ (respiration in an uncoupled state) respirations. Further, using substrate or inhibitor of a specific complex we show that the OCR via complex I and II...

Postnatal Hyperoxia Exposure Differentially Affects Hepatocytes and Liver Haemopoietic Cells in Newborn Rats

Marconi, Guya Diletta; Zara, Susi; De Colli, Marianna; Di Valerio, Valentina; Rapino, Monica; Zaramella, Patrizia; Dedja, Arben; Macchi, Veronica; De Caro, Raffaele; Porzionato, Andrea
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 12/08/2014 Português
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27.62%
Premature newborns are frequently exposed to hyperoxic conditions and experimental data indicate modulation of liver metabolism by hyperoxia in the first postnatal period. Conversely, nothing is known about possible modulation of growth factors and signaling molecules involved in other hyperoxic responses and no data are available about the effects of hyperoxia in postnatal liver haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1α (HIF-1α), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB). Experimental design of the study involved exposure of newborn rats to room air (controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the first two postnatal weeks. Immunohistochemical and Western blot analyses were performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression and decreased VEGF expression. Reduced content in reticular fibers was found in moderate and severe hyperoxia. Some other changes were specifically produced in hepatocytes by moderate hyperoxia...

Pulmonary expression of vascular endothelial growth factor (VEGF) and alveolar septation in a newborn rat model exposed to acute hypoxia and recovered under conditions of air or hyperoxia

Remesal, Ana; Pedraz, Carmen; San Feliciano, Laura; Ludeña, Dolores
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
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37.3%
Vascular endothelial growth factor (VEGF) is an endothelial cell growth factor expressed in normal lung tissue. The aim of the study was to investigate the expression of VEGF and its repercussions as regards alveolarization in the developing rat lung. We studied pulmonary VEGF expression at 0 and 14 days of life in Wistar rats. Rat pups were exposed to hypoxia for two hours during the first hours of life and recovered under conditions of hyperoxia or normoxia for a further two hours, or not recovered. The animals of the control group were only exposed to conditions of normoxia. Our results showed that VEGF was increased in the lungs of the animals that were exposed to hypoxia but we did not find any correlation with the septation. The VEGF was decreased in the lungs of animals exposed to hyperoxia after neonatal hypoxia. We observed this at 0 and 14 days of life, and it was correlated with a lower degree of alveolarization at 14 days of life. Our data suggest that hyperoxia after neonatal hypoxia at birth may give rise to a decrease in the expression of VEGF, possibly permanently, together with a reduction in alveolar development.

Nrf2 increases survival and attenuates alveolar growth inhibition in neonatal mice exposed to hyperoxia

McGrath-Morrow, Sharon; Lauer, Thomas; Yee, Min; Neptune, Enid; Podowski, Megan; Thimmulappa, Rajesh K.; O'Reilly, Michael; Biswal, Shyam
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
Português
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Increased oxidative stress is associated with perinatal asphyxia and respiratory distress in the newborn period. Induction of nuclear factor erythroid 2 p45-related factor (Nrf2) has been shown to decrease oxidative stress through the regulation of specific gene pathways. We hypothesized that Nrf2 attenuates mortality and alveolar growth inhibition in newborn mice exposed to hyperoxia. Nrf2+/+ and Nrf2−/− newborn mice were exposed to hyperoxia at 24 h. Survival was significantly less in Nrf2−/− mice exposed to 72 h of hyperoxia and returned to room air (P < 0.0001) and in Nrf2−/− mice exposed to hyperoxia for 8 continuous days (P < 0.005). To determine the response of Nrf2 target genes to hyperoxia, glutathione peroxidase 2 (Gpx2) and NAD(P)H:quinone oxidoreductase (NQO1) expression was measured from lung of newborn mice using real-time PCR. In the Nrf2+/+ mice, significant induction of lung Gpx2 and NQO1 above room air controls was found with hyperoxia. In contrast, Nrf2−/− mice had minimal induction of lung Gpx2 and NQO1 with hyperoxia. Expression of p21 and IL-6, genes not regulated by Nrf2, were also measured. IL-6 expression in Nrf2−/− lung was markedly induced by 72 h of hyperoxia in contrast to the Nrf2+/+ mice. p21 was induced in both Nrf2+/+ and Nrf2−/− lung by hyperoxia. Mean linear intercept (MLI) and mean chord length (MCL) were significantly increased in 14-day-old Nrf2−/− mice previously exposed to hyperoxia compared with Nrf2+/+ mice. The percentage of surfactant protein C (Sp-c+) type 2 alveolar cells in 14-day-old Nrf2−/− mice exposed to neonatal hyperoxia was also significantly less than Nrf2+/+ mice (P < 0.02). In summary...

Use of diffusion tensor imaging to assess the impact of normobaric hyperoxia within at-risk pericontusional tissue after traumatic brain injury

Veenith, Tonny V.; Carter, Eleanor L.; Grossac, Julia; Newcombe, Virginia F.; Outtrim, Joanne G.; Nallapareddy, Sridhar; Lupson, Victoria; Correia, Marta M.; Mada, Marius M.; Williams, Guy B.; Menon, David K.; Coles, Jonathan P.
Fonte: NPG Publicador: NPG
Tipo: Article; published version
Português
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This is the final published version of the article. It was originally published by NPG in Journal of Cerebral Blood Flow & Metabolism here: http://www.nature.com/jcbfm/journal/vaop/ncurrent/full/jcbfm2014123a.html.; Ischemia and metabolic dysfunction remain important causes of neuronal loss after head injury, and we have shown that normobaric hyperoxia may rescue such metabolic compromise. This study examines the impact of hyperoxia within injured brain using diffusion tensor imaging (DTI). Fourteen patients underwent DTI at baseline and after 1 hour of 80% oxygen. Using the apparent diffusion coefficient (ADC) we assessed the impact of hyperoxia within contusions and a 1 cm border zone of normal appearing pericontusion, and within a rim of perilesional reduced ADC consistent with cytotoxic edema and metabolic compromise. Seven healthy volunteers underwent imaging at 21%, 60%, and 100% oxygen. In volunteers there was no ADC change with hyperoxia, and contusion and pericontusion ADC values were higher than volunteers (P<0.01). There was no ADC change after hyperoxia within contusion, but an increase within pericontusion (P<0.05). We identified a rim of perilesional cytotoxic edema in 13 patients, and hyperoxia resulted in an ADC increase towards normal (P = 0.02). We demonstrate that hyperoxia may result in benefit within the perilesional rim of cytotoxic edema. Future studies should address whether a longer period of hyperoxia has a favorable impact on the evolution of tissue injury.; RCUK...

Use of diffusion tensor imaging to assess the impact of normobaric hyperoxia within at-risk pericontusional tissue following traumatic brain injury

Veenith, T. V.; Carter, E. L.; Grossac, J.; Newcombe, V. F.; Outtrim, J. G.; Nallapareddy, Sridhar; Lupson, Victoria; Correia, M. M.; Mada, Marius M.; Williams, Guy B.; Menon, David K.; Coles, J. P.
Fonte: Universidade de Cambridge Publicador: Universidade de Cambridge
Tipo: Article; accepted version
Português
Relevância na Pesquisa
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This is the final published version, which can also be viewed on the publisher's website at: http://www.nature.com/jcbfm/journal/vaop/ncurrent/full/jcbfm2014123a.html; Ischaemia and metabolic dysfunction remain important causes of neuronal loss following head injury, and we have shown that normobaric hyperoxia may rescue such metabolic compromise. This study examines the impact of hyperoxia within injured brain using diffusion tensor imaging (DTI). Fourteen patients underwent DTI at baseline and following one hour of 80% oxygen. Using the apparent diffusion coefficient (ADC) we assessed the impact of hyperoxia within contusions and a 1 cm border zone of normal appearing pericontusion, and within a rim of perilesional reduced ADC consistent with cytotoxic oedema and metabolic compromise. Seven healthy volunteers underwent imaging at 21%, 60% and 100% oxygen. In volunteers there was no ADC change with hyperoxia, and contusion and pericontusion ADC values were higher than volunteers (p < 0.01). There was no ADC change following hyperoxia within contusion, but an increase within pericontusion (p < 0.05). We identified a rim of perilesional cytotoxic oedema in 13 patients, and hyperoxia resulted in an ADC increase towards normal (p = 0.02). We demonstrate that hyperoxia may result in benefit within the perilesional rim of cytotoxic oedema. Future studies should address whether a longer period of hyperoxia has a favourable impact on the evolution of tissue injury.; Dr TV Veenith was supported by clinical research training fellowship from National institute of Academic Anaesthesia and Raymond Beverly Sackler studentship. VFJN is supported by an NIHR academic clinical fellowship. JPC was supported by Wellcome trust project grant. DKM is supported by an NIHR Senior Investigator Award. This work was supported by a Medical Research Council (UK) Program Grant (Acute brain injury: heterogeneity of mechanisms...