Mild Hyperoxia Research Articles

Association between Early Hyperoxia and Neurologic Outcome in Patient with High Grade Aneurysmal Subarachnoid Hemorrhage

Background: Oxygenation support is a common practice in patients with aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to analyze the association between early hyperoxia and the neurological outcome in patients presenting a High Grade SAH, using the modified Rankin Scale (mRS) at 6 months. Methods: We retrospectively analyzed data of SAH in a single center, retrospective, observational study. The inclusion criteria were patients’ ≥ 18 years-old, under mechanical ventilation upon admission to the intensive care unit (ICU) and presenting an aneurysmal SAH with a WFNS score ≥3. Hyperoxia was defined as PaO2 > 120 mmHg and classified into 3 subgroups: mild (121-200 mmHg), moderate (201-300 mmHg) and severe (> 300 mmHg). Patients with a 6 months-mRS >3 were considered as having a poor outcome. Results: One hundred and thirty-nine patients with aneurysmal SAH were included. 82% of patients were exposed to hyperoxia with predominance of mild hyperoxia (42.8%). A higher yet non-statistical, poor neurologic outcome was identified in the hyperoxic compared to normoxic group (72% vs. 87.7% OR 2.8 [1.02-7.71], p 0.12). Following a multivariate analysis, a statistical trend was identified between the hyperoxic group and a 6-month poor neurological outcome (OR 2.84, 95% CI, 0.99-8.19; p=0.052), but no statistical association was found with delayed cerebral ischemia (OR 1.68, 95% CI, 0.5-5.71, p=0.39) nor with 28-day mortality (OR 2.17, 95% CI, 0.82-5.75, p=0.11). Conclusions: Our findings suggest a statistical trend between early hyperoxia and a poor neurological outcome at 6 months, in patients with a high grade aneurysmal SAH admitted to the ICU. Further, large-scale studies are required to fully evaluate the effects of hyperoxia.

Impact of early hyperoxia on 28-day in-hospital mortality in patients with myocardial injury.

IntroductionDespite relevant evidence that supplemental oxygen therapy can be harmful to patients with myocardial injury, the association between hyperoxia and the clinical outcome of such patients has not been evaluated. We assessed whether early hyperoxia negatively affects outcomes in hospitalized patients with myocardial injury.MethodsThis was a retrospective study conducted at a tertiary referral teaching hospital. Between January 2010 and December 2016, 2,376 consecutive emergency department patients with myocardial injury, defined as a peak troponin-I level ≥ 0.2 ng/mL, within the first 24 hours of presentation were included. The metrics used to define hyperoxia were the maximum average partial pressure of oxygen (PaO2MAX), average partial pressure of oxygen (PaO2AVG), and area under the curve during the first 24 hours (AUC24). The association between early hyperoxia within 24 hours after presentation and clinical outcomes was evaluated using multiple imputation and logistic regression analysis. The primary outcome was 28-day in-hospital mortality. The secondary outcomes were new-onset cardiovascular, coagulation, hepatic, renal, and respiratory dysfunctions (sequential organ failure sub-score ≥ 2).ResultsCompared with normoxic patients, the adjusted odds ratios (ORs) for PaO2MAX, PaO2AVG, and AUC24 were 1.55 (95% confidence interval (CI) 1.05–2.27; p = 0.026), 2.13 (95% CI 1.45–3.12; p = 0.001), and 1.73 (95% CI 1.15–2.61; p = 0.008), respectively, in patients with mild hyperoxia and 6.01 (95% CI 3.98–9.07; p < 0.001), 8.92 (95% CI 3.33–23.88; p < 0.001), and 7.32 (95% CI 2.72–19.70; p = 0.001), respectively, in patients with severe hyperoxia. The incidence of coagulation and hepatic dysfunction (sequential organ failure sub-score ≥ 2) was significantly higher in the mild and severe hyperoxia group.ConclusionsHyperoxia during the first 24 hours of presentation is associated with an increased 28-day in-hospital mortality rate and risks of coagulation and hepatic dysfunction in patients with myocardial injury.

Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care.

Emerging evidence has shown the potential risks of arterial hyperoxia, but the lack of a clinical definition and methodologic limitations hamper the interpretation and clinical relevance of previous studies. Our purpose was to evaluate previously used and newly constructed metrics of arterial hyperoxia and systematically assess their association with clinical outcomes in different subgroups in the ICU. Observational cohort study. Three large tertiary care ICUs in the Netherlands. A total of 14,441 eligible ICU patients. None. In total, 295,079 arterial blood gas analyses, including the PaO2, between July 2011 and July 2014 were extracted from the patient data management system database. Data from all admissions with more than one PaO2 measurement were supplemented with anonymous demographic and admission and discharge data from the Dutch National Intensive Care Evaluation registry. Mild hyperoxia was defined as PaO2 between 120 and 200 mm Hg; severe hyperoxia as PaO2 greater than 200 mm Hg. Characteristics of existing and newly constructed metrics for arterial hyperoxia were examined, and the associations with hospital mortality (primary outcome), ICU mortality, and ventilator-free days and alive at day 28 were retrospectively analyzed using regression models in different subgroups of patients. Severe hyperoxia was associated with higher mortality rates and fewer ventilator-free days in comparison to both mild hyperoxia and normoxia for all metrics except for the worst PaO2. Adjusted effect estimates for conditional mortality were larger for severe hyperoxia than for mild hyperoxia. This association was found both within and beyond the first 24 hours of admission and was consistent for large subgroups. The largest point estimates were found for the exposure identified by the average PaO2, closely followed by the median PaO2, and these estimates differed substantially between subsets. Time spent in hyperoxia showed a linear and positive relationship with hospital mortality. Our results suggest that we should limit the PaO2 levels of critically ill patients within a safe range, as we do with other physiologic variables. Analytical metrics of arterial hyperoxia should be judiciously considered when interpreting and comparing study results and future studies are needed to validate our findings in a randomized fashion design.

Severity of hyperoxia as a risk factor in patients undergoing on-pump cardiac surgery.

Background.Hyperoxia has long been perceived as a desirable or at least an inevitable part of cardiopulmonary bypass. Recent evidence suggest that it might have multiple detrimental effects on patient homeostasis. The aim of the study was to identify the determinants of supra-physiological values of partial oxygen pressure during on-pump cardiac surgery and to assess the impact of hyperoxia on clinical outcomes.Materials and methods.Retrospective data analysis of the institutional research database was performed to evaluate the effects of hyperoxia in patients undergoing elective cardiac surgery with cardiopulmonary bypass, 246 patients were included in the final analysis. Patients were divided in three groups: mild hyperoxia (MHO, PaO2 100–199 mmHg), moderate hyperoxia (MdHO, PaO2 200–299 mmHg), and severe hyperoxia (SHO, PaO2 >300 mmHg). Postoperative complications and outcomes were defined according to standardised criteria of the Society of Thoracic Surgeons.Results.The extent of hyperoxia was more immense in patients with a lower body mass index (p = 0.001) and of female sex (p = 0.005). A significant link between severe hyperoxia and a higher incidence of infectious complications (p – 0.044), an increased length of hospital stay (p – 0.044) and extended duration of mechanical ventilation (p < 0.001) was confirmed.Conclusions.Severe hyperoxia is associated with an increased incidence of postoperative infectious complications, prolonged mechanical ventilation, and increased hospital stay.

Brain adaptation to hypoxia and hyperoxia in mice

AimsHyperoxic breathing might lead to redox imbalance and signaling changes that affect cerebral function. Paradoxically, hypoxic breathing is also believed to cause oxidative stress. Our aim is to dissect the cerebral tissue responses to altered O2 fractions in breathed air by assessing the redox imbalance and the recruitment of the hypoxia signaling pathways. ResultsMice were exposed to mild hypoxia (10%O2), normoxia (21%O2) or mild hyperoxia (30%O2) for 28 days, sacrificed and brain tissue excised and analyzed. Although one might expect linear responses to %O2, only few of the examined variables exhibited this pattern, including neuroprotective phospho- protein kinase B and the erythropoietin receptor. The major reactive oxygen species (ROS) source in brain, NADPH oxidase subunit 4 increased in hypoxia but not in hyperoxia, whereas neither affected nuclear factor (erythroid-derived 2)-like 2, a transcription factor that regulates the expression of antioxidant proteins. As a result of the delicate equilibrium between ROS generation and antioxidant defense, neuron apoptosis and cerebral tissue hydroperoxides increased in both 10%O2 and 30%O2, as compared with 21%O2. Remarkably, the expression level of hypoxia-inducible factor (HIF)−2α (but not HIF-1α) was higher in both 10%O2 and 30%O2 with respect to 21%O2 InnovationComparing the in vivo effects driven by mild hypoxia with those driven by mild hyperoxia helps addressing whether clinically relevant situations of O2 excess and scarcity are toxic for the organism. ConclusionProlonged mild hyperoxia leads to persistent cerebral damage, comparable to that inferred by prolonged mild hypoxia. The underlying mechanism appears related to a model whereby the imbalance between ROS generation and anti-ROS defense is similar, but occurs at higher levels in hypoxia than in hyperoxia.

Effects of Oxygen Concentrations on Postresuscitation Myocardial Oxidative Stress and Myocardial Function in a Rat Model of Cardiopulmonary Resuscitation.

Lipid peroxidation induced by free-radical species plays a prominent role in myocardial injury following ischemia and reperfusion. However, there is a lack of data in different oxygen concentrations on myocardial lipid peroxidation during the early phase of reperfusion. In this study, we investigated whether ventilation with medium or normal concentration of oxygen would decrease the severity of myocardial lipid peroxidation and postresuscitation myocardial dysfunction. Prospective, randomized, controlled experimental study. University-affiliated animal research institution. Sixty-three healthy male Sprague-Dawley rats. Animals were randomized into three groups: 1) 100% group, 2) 50% group, and 3) 21% group. Ventricular fibrillation was induced and untreated for 8 minutes, and defibrillation was attempted after 8 minutes of cardiopulmonary resuscitation. Ventilation with 100%, 50%, or 21% oxygen was initiated in all groups during cardiopulmonary resuscitation and 1 hour following the return of spontaneous circulation. Normoxic ventilation was maintained thereafter. Myocardial function, including ejection fraction and myocardial performance index, were measured at baseline, 4, or 72 hours after resuscitation. Blood samples were drawn at baseline, 15 minutes, 1, 4, or 72 hours after resuscitation for the measurements of blood gas or biomarkers. Significantly better myocardial function and longer duration of survival were observed in the 50% group. Compared with the 21% and 100% groups, a mild hyperoxia and greater oxygen extraction with lower 8-iso-prostaglandin F2α were observed in the 50% group. Pearson correlation analysis confirmed that 8-iso-prostaglandin F2α was positively correlated with myocardial performance index at 4 hours postresuscitation. In a rat model of cardiac arrest and resuscitation, ventilation with 50% inspired oxygen during early postischemic reperfusion phase contributed to a decreased lipid peroxidation and a better myocardial function and duration of survival.

Oxygen changes drive non-uniform scaling in Drosophila melanogaster embryogenesis

We previously demonstrated that, while changes in temperature produce dramatic shifts in the time elapsed during Drosophila melanogaster embryogenesis, the relative timing of events within embryogenesis does not change. However, it was unclear if this uniform scaling is an intrinsic property of developing embryos, or if it is specific to thermal fluctuations. To investigate this, here we characterize the embryonic response to changes in oxygen concentration, which also impact developmental rate, using time-lapse imaging, and find it fundamentally different from the temperature response. Most notably, changes in oxygen levels drive developmental heterochrony, with the timing of several morphological processes showing distinct scaling behaviors. Gut formation is severely slowed by decreases in oxygen, while head involution and syncytial development are less impacted than the rest of development, and the order of several developmental landmarks is inverted at different oxygen levels. These data reveal that the uniform scaling seen with changes in temperature is not a trivial consequence of adjusting developmental rate. The developmental rate changes produced by changing oxygen concentrations dwarf those induced by temperature, and greatly impact survival. While extreme temperatures increase early embryo mortality, mild hypoxia increases arrest and death during mid-embryogenesis and mild hyperoxia increases survival over normoxia.

Oxygen changes drive non-uniform scaling in Drosophila melanogaster embryogenesis.

We previously demonstrated that, while changes in temperature produce dramaticshifts in the time elapsed during Drosophila melanogaster embryogenesis, therelative timing of events within embryogenesis does not change. However, it wasunclear if this uniform scaling is an intrinsic property of developing embryos, orif it is specific to thermal fluctuations. To investigate this, here we characterizethe embryonic response to changes in oxygen concentration, which also impactdevelopmental rate, using time-lapse imaging, and find it fundamentally differentfrom the temperature response. Most notably, changes in oxygen levels drivedevelopmental heterochrony, with the timing of several morphological processesshowing distinct scaling behaviors. Gut formation is severely slowed by decreasesin oxygen, while head involution and syncytial development are less impactedthan the rest of development, and the order of several developmental landmarksis inverted at different oxygen levels. These data reveal that the uniform scalingseen with changes in temperature is not a trivial consequence of adjusting developmentalrate. The developmental rate changes produced by changing oxygenconcentrations dwarf those induced by temperature, and greatly impact survival.While extreme temperatures increase early embryo mortality, mild hypoxia increasesarrest and death during mid-embryogenesis and mild hyperoxia increasessurvival over normoxia.

Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure

Preterm infants often require supplemental oxygen due to lung immaturity, but hyperoxia can contribute to an increased risk of respiratory illness later in life. Our aim was to compare the effects of mild and moderate levels of neonatal hyperoxia on markers of pulmonary oxidative stress and inflammation and on lung architecture; both immediate and persistent effects were assessed. Neonatal mice (C57BL6/J) were raised in either room air (21% O2), mild (40% O2), or moderate (65% O2) hyperoxia from birth until postnatal day 7 (P7d). The mice were killed at either P7d (immediate effects) or lived in air until adulthood (P56d, persistent effects). We enumerated macrophages in lung tissue at P7d and immune cells in bronchoalveolar lavage fluid (BALF) at P56d. At P7d and P56d, we assessed pulmonary oxidative stress [heme oxygenase-1 (HO-1) and nitrotyrosine staining] and lung architecture. The data were interrogated for sex differences. At P7d, HO-1 gene expression was greater in the 65% O2 group than in the 21% O2 group. At P56d, the area of nitrotyrosine staining and number of immune cells were greater in the 40% O2 and 65% O2 groups relative to the 21% O2 group. Exposure to 65% O2, but not 40% O2, led to larger alveoli and lower tissue fraction in the short term and to persistently fewer bronchiolar-alveolar attachments. Exposure to 40% O2 or 65% O2 causes persistent increases in pulmonary oxidative stress and immune cells, suggesting chronic inflammation within the adult lung. Unlike 65% O2, 40% O2 does not affect lung architecture.

Airway Hyperreactivity Is Delayed after Mild Neonatal Hyperoxic Exposure

Background: Wheezing disorders are prominent in former preterm infants beyond the neonatal period. Objectives: We used a neonatal mouse model to investigate the time course of airway hyperreactivity in response to mild (40% oxygen) or severe (70% oxygen) neonatal hyperoxia. Methods: After hyperoxic exposure during the first week of postnatal life, we measured changes in airway reactivity using the in vitro living lung slice preparation at the end of exposure [postnatal day 8 (P8)] and 2 weeks later (P21). This was accompanied by measures of smooth muscle actin, myosin light chain (MLC) and alveolar morphology. Results: Neither mild nor severe hyperoxia exposure affected airway reactivity to methacholine at P8 compared to normoxic controls. In contrast, airway reactivity was enhanced at P21 in mice exposed to mild (but not severe) hyperoxia, 2 weeks after exposure ended. This was associated with increased airway α-smooth muscle actin expression at P21 after 40% oxygen exposure without a significant increase in MLC. Alveolar morphology via radial alveolar counts was comparably diminished by both 40 and 70% oxygen at both P8 and P21. Conclusions: These data demonstrate that early mild hyperoxia exposure causes a delayed augmentation of airway reactivity, suggesting a long-term alteration in the trajectory of airway smooth muscle development and consistent with resultant symptomatology.

Physiological and morphological effects of severe hypoxia, hypoxia and hyperoxia in juvenile turbot (Scophthalmus maximusL.)

We studied the physiological status of juvenile turbot (Scophthalmus maximus L.) under severe hypoxia (1 and 2 mg/L dissolved oxygen, DO), hypoxia (3 and 5 mg/L DO), hyperoxia (11 and 14 mg/L DO) and normoxia (7 mg/L DO, control) conditions. The respiratory rates, haematology parameters, acid–base balance status and gill structure were analysed to find the effects of different DO concentration on turbot. Fish mortality was only observed under severe hypoxia conditions. Severe hypoxia caused an increase in respiratory rates and red blood cell counts, as well as an increase in haemoglobin and haematocrit levels in the fish. In fish exposed to hypoxia conditions, the respiratory rate increased overall as the DO concentration decreased. Lower pCO2 and HCO3− levels led to a high blood pH, while the pO2 remained stable. In hyperoxia groups, respiratory rate decreased as the DO concentration increased. The levels of pCO2 and HCO3− significantly increased (P < 0.05), while the pO2 level and blood pH did not change obviously. The gill structure was damaged after prolonged exposure to hyperoxia, but no obvious damage was found in hypoxia groups. The fish that survived the hypoxia or hyperoxia treatment were able to restore the structural integrity of the gills after 14 days' recovery. The results suggest that juvenile turbots can tolerate a wide range of DO concentrations. However, even mild hyperoxia condition (11 mg/L DO), which is widely used in fish culture, has adverse effects on juvenile turbot physiology.

Platinized aligned carbon nanotube-sheathed carbon fiber microelectrodes for in vivo amperometric monitoring of oxygen.

The abnormal level of O2 could disturb various neurochemical processes and even induce neural injury and brain dysfunction. In order to assess critical roles of O2 in the neurochemical processes, it is essential to perform in vivo monitoring of the dynamic changes of O2. In this study, we develop a new electrochemical method for selectively monitoring O2 in vivo, using platinized vertically aligned carbon nanotube (VACNT)-sheathed carbon fibers (Pt/VACNT-CFs) as the electrodes. The VACNT-sheathed CFs (VACNT-CFs) are produced via the pyrolysis of iron phthalocyanine (FePc) on the surface of CFs, followed by electrochemical deposition of platinum nanoparticles to form Pt/VACNT-CFs. The resulting Pt/VACNT-CF microelectrodes exhibit fast overall kinetics for the O2 reduction via a four-electron reduction process without the formation of toxic H2O2 intermediate. Consequently, effective and selective electrochemical methods are developed for the measurements of O2 in rat brain with the Pt/VACNT-CF microelectrodes, even in the presence of some species at their physiological levels, such as ascorbic acid, dopamine, uric acid, 5-hydroxytryptamine, and of the O2 fluctuation in rat brain in the early stage of global cerebral ischemia/reperfusion, mild hyperoxia, and hypoxia induced by exposing the animal, for a short time, to O2 and N2, respectively, and hindfeet pinch. The use of VACNT-CF as the support for Pt effectively improves the stability of Pt, as compared with the bare CF support, while the FePc pyrolysis ensures the VACNT-CFs to be reproducibly produced. Thus, this study offers a novel and reliable strategy for preparing new microelectrodes for in vivo monitoring of O2 in various physiological processes with a high sensitivity and selectivity.

Profiling of Target Genes that Regulate EP-Induced Growth Inhibition of H460 through the Transcriptional and Proteomic Analysis

Mechanical forces from outside the cells such as compression, stretching or shear stress are well known to participate in various cellular processes. Elevated pressure (EP) is an extrinsic mechanical force which induces mild hyperoxia under 2 ATA of pressure when applied to cells or whole tissues. To evaluate the effect of EP, we tested cell growth in H460 non-small lung carcinoma cells during 48 hours. Cell growth was inhibited over 25% without DNA damage and cell death, and colony formation was also suppressed at EP compared to cells cultured in conventional cell incubator.To identify target molecules that induces cell growth inhibition, we performed transcriptional and phospho-proteomic analysis with phospho-MAPK array. By transcriptome analysis using RNA-sequencing, we identified that 545 genes has increased and 304 genes has decreased over 2 folds in cells under EP. Many genes were related with membrane proteins, ECM molecules and cytoskeleton molecules. Among them we confirmed the gene including IGFBP5, P2RY6 and IL1R2 by real-time PCR. Among MAPK proteins only Erk phosphorylation was decreased, but not Akt, JNK and MKK3/6 under the exposure of EP for 4 hours. Phospho-proteomic analysis with 2D and PMF (Peptide mass fingerprint) showed increased phosphorylation of 41 proteins including GNB2L1 (Guanine Nucleotide Binding Protein) and decreased phosphorylation of 14 proteins including HELLS (helicase, lymphoid-specific) which are known to regulate cell growth and Erk activation.Our results suggested that EP inhibits cell growth of H460 cancer cells through regulation of various molecules related with cell growth including Erk, IGFBP and GNB2L1.(Medical Research Center for Environmental Toxico-Genomics and Proteomics Project, No.20090091416).

Hyperoxia-Triggered Aversion Behavior in Drosophila Foraging Larvae Is Mediated by Sensory Detection of Hydrogen Peroxide

Reactive oxygen species (ROS) in excess have been implicated in numerous chronic illnesses, including asthma, diabetes, aging, cardiovascular disease, and neurodegenerative illness. However, at lower concentrations, ROS can also serve essential routine functions as part of cellular signal transduction pathways. As products of atmospheric oxygen, ROS-mediated signals can function to coordinate external environmental conditions with growth and development. A central challenge has been a mechanistic distinction between the toxic effects of oxidative stress and endogenous ROS functions occurring at much lower concentrations. Drosophila larval aerotactic behavioral assays revealed strong developmentally regulated aversion to mild hyperoxia mediated by H2O2-dependent activation of class IV multidendritic (mdIV) sensory neurons expressing the Degenerin/epithelial Na+ channel subunit, Pickpocket1 (PPK1). Electrophysiological recordings in foraging-stage larvae (78–84 h after egg laying [AEL]) demonstrated PPK1-dependent activation of mdIV neurons by nanomolar levels of H2O2 well below levels normally associated with oxidative stress. Acute sensitivity was reduced > 100-fold during the larval developmental transition to wandering stage (> 96 h AEL), corresponding to a loss of hyperoxia aversion behavior during the same period. Degradation of endogenous H2O2 by transgenic overexpression of catalase in larval epidermis caused a suppression of hyperoxia aversion behavior. Conversely, disruption of endogenous catalase activity using a UAS-CatRNAi transposon resulted in an enhanced hyperoxia-aversive response. These results demonstrate an essential role for low-level endogenous H2O2 as an environment-derived signal coordinating developmental behavioral transitions.

Endothelial colony-forming cell conditioned media promote angiogenesis in vitro and prevent pulmonary hypertension in experimental bronchopulmonary dysplasia

Late-outgrowth endothelial colony-forming cells (ECFCs), a type of circulating endothelial progenitor cell (EPC), may contribute to pulmonary angiogenesis during development. Cord blood ECFCs from preterm newborns proliferate more rapidly than term ECFCs but are more susceptible to the adverse effects of hyperoxia. Recent studies suggest that bone marrow-derived EPCs protect against experimental lung injury via paracrine mechanisms independent of vascular engraftment. To determine whether human umbilical cord blood ECFCs from preterm and term newborns have therapeutic benefit in experimental neonatal lung injury, we isolated cord blood ECFCs from full-term and preterm newborns and prepared ECFC-conditioned medium (CM) to test its therapeutic benefit on fetal pulmonary artery endothelial cell (PAEC) proliferation and function as well as alveolar type 2 (AT2) cell growth. PAECs and AT2 cells were isolated from late-gestation fetal sheep. Additionally, we administered both ECFCs and ECFC-CM to bleomycin-exposed newborn rats, an experimental model of bronchopulmonary dysplasia (BPD). Both term ECFC-CM and preterm ECFC-CM promoted cell growth and angiogenesis in vitro. However, when ECFC-CM was collected during exposure to mild hyperoxia, the benefit of preterm ECFC-CM was no longer observed. In the bleomycin model of BPD, treatment with ECFC-CM (or CM from mature EC) effectively decreased right ventricular hypertrophy but had no effect on alveolar septation. We conclude that term ECFC-CM is beneficial both in vitro and in experimental BPD. During oxidative stress, preterm ECFC-CM, but not term ECFC-CM, loses its benefit. The inability of term ECFC-CM to promote alveolarization may limit its therapeutic potential.

Anthocyanins protect human endothelial cells from mild hyperoxia damage through modulation of Nrf2 pathway

The detrimental effects of high oxygen supplementation have been widely reported. Conversely, few is known about the effects of exposure to mild hyperoxic conditions, an interesting issue since the use of oxygen-enriched mixture is now increasingly used in clinical practice and especially for professional and recreational reasons. Our study investigated if in vitro exposure of human umbilical vein endothelial cells (HUVECs) to moderate hyperoxia (O2 32%) induces cellular alterations, measured as changes in cell signaling pathways. Furthermore, by means of an ex vivo experimental model where human volunteers were used as bioreactors, we studied whether anthocyanin metabolites are able to protect HUVECs against mild hyperoxia-induced damage. We observed that the cytotoxic effect of mild hyperoxia came along with a significant decrease in nuclear accumulation of the transcription factor Nrf2, as well as in the expression of Nrf2-regulated antioxidant and cytoprotective genes. Furthermore, under normoxic conditions, anthocyanin metabolites appeared able to activate the Nrf2 pathway, through the involvement of specific kinases (ERK1/2); this adaptive effect may explain the protective effect observed in mild hyperoxia-exposed HUVECs following anthocyanin pretreatment. This study confirms that dietary anthocyanins and/or their metabolites can protect endothelial cells against mild hyperoxia-induced alterations acting as cell signaling modulators.

Growth inhibition of H460 non-small lung carcinoma cells without cytotoxicity by mild hyperoxia under elevated pressure (2ATA)

Growth inhibition of H460 non-small lung carcinoma cells without cytotoxicity by mild hyperoxia under elevated pressure (2ATA)

PPKCα mediated-HIF-1α activation related to the morphological modifications occurring in neonatal myocardial tissue in response to severe and mild hyperoxia

In premature babies birth an high oxygen level exposure can occur and newborn hyperoxia exposure can be associated with free radical oxygen release with impairment of myocardial function, while in adult animal models short exposure to hyperoxia seems to protect heart against ischemic injury. Thus, the mechanisms and consequences which take place after hyperoxia exposure are different and related to animals age. The aim of our work has been to analyze the role played by HIF-1α in the occurrence of the morphological modifications upon hyperoxia exposure in neonatal rat heart. Hyperoxia exposure induces connective compartment increase which seems to allow enhanced blood vessels growth. An increased hypoxia inducible factor-1α (HIF-1α) translocation and vascular endothelial growth factor (VEGF) expression has been found upon 95% oxygen exposure to induce morphological modifications. Upstream pPKC-α expression increase in newborn rats exposed to 95% oxygen can suggest PKC involvement in HIF-1α activation. Since nitric oxide synthase (NOS) are involved in heart vascular regulation, endothelial NOS (e-NOS) and inducible NOS (i-NOS) expression has been investigated: a lower eNOS and an higher iNOS expression has been found in newborn rats exposed to 95% oxygen related to the evidence that hyperoxia provokes a systemic vasoconstriction and to the iNOS pro-apoptotic action, respectively. The occurrence of apoptotic events, evaluated by TUNEL and Bax expression analyses, seems more evident in sample exposed to severe hyperoxia. All in all such results suggest that in newborn rats hyperoxia can trigger oxygen free radical mediated membrane injury through a pPKCα mediated HIF-1α signalling system, even though specificity of such response could be obtained by in vivo administration to the rats of specific inhibitors of PKCα. This intracellular signalling can switch molecular events leading to blood vessels development in parallel to pro-apoptotic events due to an immature anti-oxidant defensive system in newborn rat hearts.

Larval rearing environment influences the physiological adaptation in juvenile Atlantic cod, Gadus morhua

Juvenile Atlantic cod, Gadus morhua, that had been fed rotifers as larvae (R group) had significantly lower growth rates (SGR) at high-ambient ammonia (UIA = 115–120 μg l−1) than did juveniles that had been first fed with natural zooplankton (Z group). Overall specific growth rates (SGRs) were 5–11% higher in the Z group at the control ammonia (UIA = 1–2 μg l−1) treatments. An interaction between larval rearing history, oxygen and ammonia levels was found, as SGR decreased with decreasing oxygen levels at high ammonia in the R group, while the SGR in the Z group were less affected by hypoxia. At high-ambient ammonia, the SGRs were 5% (mild hyperoxia, 101–104% O2 in effluent water), 28% (normoxia, 83–88% O2 in effluent water) and 86% (hypoxia, 57–69% O2 in effluent water) higher in the Z group, compared to the R group. The present findings indicate that larval rearing environment could influence the adaptability to environmental changes and growth performance during later juvenile stage in cod. These findings have implications for the optimization of Atlantic cod culture.

Cytoprotective activity of elevated static pressure against oxidative stress in normal human fibroblasts

DNA damage in normal cells by reactive oxygen species can trigger cellular senescence and tumorigenesis. Therefore, many strategies have been developed to inhibit DNA damage and identify molecules that can prevent various oxidative stress-related diseases, including cancer. To investigate the effect of pressure, preconditioning with two types of atmospheric pressure (hyperbaric mild hyperoxia compressed with air (EP) and hyperbaric normoxia with nitrogen gas (HN)) was applied to normal human lung fibroblasts (WI-38) for 1 or 3 days, and then cells were treated with hydrogen peroxide to induce oxidative damage. Here, we have elucidated two types of pressure that can protect WI-38 cells from oxidative stress-induced DNA damage. To profile the expression of genes that contribute to the cytoprotective effects of the pressures, microarray analyses were performed. Extracellular matrix-, cell adhesion-, and cell cycle-related genes were highly involved in the cytoprotective effects of the pressures. Among the significantly expressed genes, fibronectin was the most inducible in WI-38 cells under the cytoprotective conditions against oxidative damage. Additionally, cellular fibronectin, and not the secreted isoform, acted as a cytoprotective marker at these pressures. Together, these findings suggest that elevated static pressures exhibit cytoprotective activity against oxidative stress-induced DNA damage by inducing cellular fibronectin.