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Oxygen Variations

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 21986

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Prof. Dr. Costantino Balestra

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Guest Editor

Environmental, Occupational & Ageing Physiology Laboratory, Haute Ecole Bruxelles-Brabant (HE2B), Brussels, Belgium
Interests: integrative physiology; oxygen; challenging environments; hyperbaric; hypobaric; hyperoxia; hypoxia; normobaric oxygen paradox
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Fabio Virgili

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Guest Editor

Research Centre for Food and Nutrition, Council for Agricultural Research and Economics, Rome, Italy
Interests: vitamin; molecules of nutritional interest on transcriptional control of gene expression; gene variants; nutrigenomics

Prof. Dr. Simona Mrakic-Sposta

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Guest Editor

National Research Council, Institute of Clinical Physiology, Milan, Italy
Interests: oxidative stress; redox state; inflammation; hypoxia; hyperoxia; extreme environments; normo-hypo-hyperbaric
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For over 100 years, our focus in studying human physiology has been aimed at steady states. Understandably, this was a clear need, since we wanted to reassure ourselves of the validity of measurements and the stability of the assessments that were performed. Moreover, the measurement systems that we used were slow and unstable, and a long calibration or “warm up” of instruments was needed to stabilize the measurements. This trend has changed in recent years. Our systems are now fast and stable enough to ensure accurate measurements even in very short timeframes. This opens up a wide range of new approaches and scientific paradigms. This means that research at present and in the future can focus on changes, or unsteady states.

We want to aim towards the future with this new Special Issue of the International Journal of Molecular Sciences within the Biochemistry & Molecular Biology section and particularly on Oxygen Changes or Deltas. We strongly believe that even fast or minute oxygen changes can be very powerful triggers in different adaptive cellular mechanisms. Every change in PO2, whether positive of negative, is of interest in this topic. We want to overcome the idea of hyperoxia or hypoxia, but rather focus on deltas and variations within all ranges, including hypoxic, hyperoxic, hypobaric, hyperbaric, etc. Every contribution on these topics will be welcomed.

Prof. Dr. Costantino Balestra
Prof. Dr. Fabio Virgili
Prof. Dr. Simona Mrakic-Sposta
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hypoxia
hyperoxia
normoxia
biochemichal response
integrative approach
normo-hypo-hyperbaric
molecular research
genes expression
adaptive reactions
extreme environments

Published Papers (11 papers)

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Editorial

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8 pages, 844 KiB

Open AccessEditorial

Oxygen Variations—Insights into Hypoxia, Hyperoxia and Hyperbaric Hyperoxia—Is the Dose the Clue?

by Costantino Balestra, Simona Mrakic-Sposta and Fabio Virgili

Int. J. Mol. Sci. 2023, 24(17), 13472; https://doi.org/10.3390/ijms241713472 - 30 Aug 2023

Cited by 6 | Viewed by 1439

Abstract

Molecular oxygen (O₂) is one of the four most important elements on Earth (alongside carbon, nitrogen and hydrogen); aerobic organisms depend on it to release energy from carbon-based molecules [...] Full article

(This article belongs to the Special Issue Oxygen Variations)

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Research

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14 pages, 1383 KiB

Open AccessArticle

Oxidative Stress Response Kinetics after 60 Minutes at Different (1.4 ATA and 2.5 ATA) Hyperbaric Hyperoxia Exposures

by Clément Leveque, Simona Mrakic Sposta, Sigrid Theunissen, Peter Germonpré, Kate Lambrechts, Alessandra Vezzoli, Gerardo Bosco, Morgan Lévénez, Pierre Lafère, François Guerrero and Costantino Balestra

Int. J. Mol. Sci. 2023, 24(15), 12361; https://doi.org/10.3390/ijms241512361 - 02 Aug 2023

Cited by 7 | Viewed by 1476

Abstract

Hyperbaric oxygen therapy (HBOT) is a therapeutical approach based on exposure to pure oxygen in an augmented atmospheric pressure. Although it has been used for years, the exact kinetics of the reactive oxygen species (ROS) between different pressures of hyperbaric oxygen exposure are still not clearly evidenced. In this study, the metabolic responses of hyperbaric hyperoxia exposures for 1 h at 1.4 and 2.5 ATA were investigated. Fourteen healthy non-smoking subjects (2 females and 12 males, age: 37.3 ± 12.7 years old (mean ± SD), height: 176.3 ± 9.9 cm, and weight: 75.8 ± 17.7 kg) volunteered for this study. Blood samples were taken before and at 30 min, 2 h, 24 h, and 48 h after a 1 h hyperbaric hyperoxic exposure. The level of oxidation was evaluated by the rate of ROS production, nitric oxide metabolites (NOx), and the levels of isoprostane. Antioxidant reactions were assessed through measuring superoxide dismutase (SOD), catalase (CAT), cysteinylglycine, and glutathione (GSH). The inflammatory response was measured using interleukine-6, neopterin, and creatinine. A short (60 min) period of mild (1.4 ATA) and high (2.5 ATA) hyperbaric hyperoxia leads to a similar significant increase in the production of ROS and antioxidant reactions. Immunomodulation and inflammatory responses, on the contrary, respond proportionally to the hyperbaric oxygen dose. Further research is warranted on the dose and the inter-dose recovery time to optimize the potential therapeutic benefits of this promising intervention. Full article

(This article belongs to the Special Issue Oxygen Variations)

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14 pages, 1534 KiB

Open AccessArticle

Oxidative Stress Response Kinetics after 60 Minutes at Different Levels (10% or 15%) of Normobaric Hypoxia Exposure

by Clément Leveque, Simona Mrakic Sposta, Sigrid Theunissen, Peter Germonpré, Kate Lambrechts, Alessandra Vezzoli, Maristella Gussoni, Morgan Levenez, Pierre Lafère, François Guerrero and Costantino Balestra

Int. J. Mol. Sci. 2023, 24(12), 10188; https://doi.org/10.3390/ijms241210188 - 15 Jun 2023

Cited by 6 | Viewed by 1206

Abstract

In this study, the metabolic responses of hypoxic breathing for 1 h to inspired fractions of 10% and 15% oxygen were investigated. To this end, 14 healthy nonsmoking subjects (6 females and 8 males, age: 32.2 ± 13.3 years old (mean ± SD), height: 169.1 ± 9.9 cm, and weight: 61.6 ± 16.2 kg) volunteered for the study. Blood samples were taken before, and at 30 min, 2 h, 8 h, 24 h, and 48 h after a 1 h hypoxic exposure. The level of oxidative stress was evaluated by considering reactive oxygen species (ROS), nitric oxide metabolites (NOx), lipid peroxidation, and immune-inflammation by interleukin-6 (IL-6) and neopterin, while antioxidant systems were observed in terms of the total antioxidant capacity (TAC) and urates. Hypoxia abruptly and rapidly increased ROS, while TAC showed a U-shape pattern, with a nadir between 30 min and 2 h. The regulation of ROS and NOx could be explained by the antioxidant action of uric acid and creatinine. The kinetics of ROS allowed for the stimulation of the immune system translated by an increase in neopterin, IL-6, and NOx. This study provides insights into the mechanisms through which acute hypoxia affects various bodily functions and how the body sets up the protective mechanisms to maintain redox homeostasis in response to oxidative stress. Full article

(This article belongs to the Special Issue Oxygen Variations)

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11 pages, 601 KiB

Open AccessArticle

Elevations of Extracellular Vesicles and Inflammatory Biomarkers in Closed Circuit SCUBA Divers

by Awadhesh K. Arya, Costantino Balestra, Veena M. Bhopale, Laura J. Tuominen, Anne Räisänen-Sokolowski, Emmanuel Dugrenot, Erwan L’Her, Abid R. Bhat and Stephen R. Thom

Int. J. Mol. Sci. 2023, 24(6), 5969; https://doi.org/10.3390/ijms24065969 - 22 Mar 2023

Cited by 6 | Viewed by 2193

Abstract

Blood-borne extracellular vesicles and inflammatory mediators were evaluated in divers using a closed circuit rebreathing apparatus and custom-mixed gases to diminish some diving risks. “Deep” divers (n = 8) dove once to mean (±SD) 102.5 ± 1.2 m of sea water (msw) for 167.3 ± 11.5 min. “Shallow” divers (n = 6) dove 3 times on day 1, and then repetitively over 7 days to 16.4 ± 3.7 msw, for 49.9 ± 11.9 min. There were statistically significant elevations of microparticles (MPs) in deep divers (day 1) and shallow divers at day 7 that expressed proteins specific to microglia, neutrophils, platelets, and endothelial cells, as well as thrombospondin (TSP)-1 and filamentous (F-) actin. Intra-MP IL-1β increased by 7.5-fold (p < 0.001) after day 1 and 41-fold (p = 0.003) at day 7. Intra-MP nitric oxide synthase-2 (NOS2) increased 17-fold (p < 0.001) after day 1 and 19-fold (p = 0.002) at day 7. Plasma gelsolin (pGSN) levels decreased by 73% (p < 0.001) in deep divers (day 1) and 37% in shallow divers by day 7. Plasma samples containing exosomes and other lipophilic particles increased from 186% to 490% among the divers but contained no IL-1β or NOS2. We conclude that diving triggers inflammatory events, even when controlling for hyperoxia, and many are not proportional to the depth of diving. Full article

(This article belongs to the Special Issue Oxygen Variations)

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20 pages, 7871 KiB

Open AccessArticle

Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury

by Rada Jeremic, Sanja Pekovic, Irena Lavrnja, Ivana Bjelobaba, Marina Djelic, Sanja Dacic and Predrag Brkic

Int. J. Mol. Sci. 2023, 24(5), 4261; https://doi.org/10.3390/ijms24054261 - 21 Feb 2023

Cited by 3 | Viewed by 1610

Abstract

A growing body of evidence suggests that hyperbaric oxygenation (HBO) may affect the activity of adult neural stem cells (NSCs). Since the role of NSCs in recovery from brain injury is still unclear, the purpose of this study was to investigate the effects of sensorimotor cortex ablation (SCA) and HBO treatment (HBOT) on the processes of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus that is the site of adult neurogenesis. Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), Sham control (S, animals that underwent the surgical procedure without opening the skull), SCA (animals in whom the right sensorimotor cortex was removed via suction ablation), and SCA + HBO (operated animals that passed HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. Using immunohistochemistry and double immunofluorescence labeling, we show that SCA causes significant loss of neurons in the DG. Newborn neurons in the subgranular zone (SGZ), inner-third, and partially mid-third of the granule cell layer are predominantly affected by SCA. HBOT decreases the SCA-caused loss of immature neurons, prevents reduction of dendritic arborization, and increases proliferation of progenitor cells. Our results suggest a protective effect of HBO by reducing the vulnerability of immature neurons in the adult DG to SCA injury. Full article

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12 pages, 2767 KiB

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The “ON-OFF” Switching Response of Reactive Oxygen Species in Acute Normobaric Hypoxia: Preliminary Outcome

by Simona Mrakic-Sposta, Maristella Gussoni, Mauro Marzorati, Simone Porcelli, Gerardo Bosco, Costantino Balestra, Michela Montorsi, Claudio Lafortuna and Alessandra Vezzoli

Int. J. Mol. Sci. 2023, 24(4), 4012; https://doi.org/10.3390/ijms24044012 - 16 Feb 2023

Cited by 5 | Viewed by 1521

Abstract

Exposure to acute normobaric hypoxia (NH) elicits reactive oxygen species (ROS) accumulation, whose production kinetics and oxidative damage were here investigated. Nine subjects were monitored while breathing an NH mixture (0.125 F_IO₂ in air, about 4100 m) and during recovery with room air. ROS production was assessed by Electron Paramagnetic Resonance in capillary blood. Total antioxidant capacity, lipid peroxidation (TBARS and 8-iso-PFG2α), protein oxidation (PC) and DNA oxidation (8-OH-dG) were measured in plasma and/or urine. The ROS production rate (μmol·min⁻¹) was monitored (5, 15, 30, 60, 120, 240 and 300 min). A production peak (+50%) was reached at 4 h. The on-transient kinetics, exponentially fitted (t_1/2 = 30 min r² = 0.995), were ascribable to the low O₂ tension transition and the mirror-like related SpO₂ decrease: 15 min: −12%; 60 min: −18%. The exposure did not seem to affect the prooxidant/antioxidant balance. Significant increases in PC (+88%) and 8-OH-dG (+67%) at 4 h in TBARS (+33%) one hour after hypoxia offset were also observed. General malaise was described by most of the subjects. Under acute NH, ROS production and oxidative damage resulted in time and SpO₂-dependent reversible phenomena. The experimental model could be suitable for evaluating the acclimatation level, a key element in the context of mountain rescues in relation to technical/medical workers who have not had enough time for acclimatization—as, for example, during helicopter flights. Full article

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13 pages, 2522 KiB

Open AccessArticle

Oxidative Stress Response’s Kinetics after 60 Minutes at Different (30% or 100%) Normobaric Hyperoxia Exposures

by Clément Leveque, Simona Mrakic-Sposta, Pierre Lafère, Alessandra Vezzoli, Peter Germonpré, Alexandre Beer, Stéphane Mievis, Fabio Virgili, Kate Lambrechts, Sigrid Theunissen, François Guerrero and Costantino Balestra

Int. J. Mol. Sci. 2023, 24(1), 664; https://doi.org/10.3390/ijms24010664 - 30 Dec 2022

Cited by 9 | Viewed by 1889

Abstract

Oxygen is a powerful trigger for cellular reactions and is used in many pathologies, including oxidative stress. However, the effects of oxygen over time and at different partial pressures remain poorly understood. In this study, the metabolic responses of normobaric oxygen intake for 1 h to mild (30%) and high (100%) inspired fractions were investigated. Fourteen healthy non-smoking subjects (7 males and 7 females; age: 29.9 ± 11.1 years, height: 168.2 ± 9.37 cm; weight: 64.4 ± 12.3 kg; BMI: 22.7 ± 4.1) were randomly assigned in the two groups. Blood samples were taken before the intake at 30 min, 2 h, 8 h, 24 h, and 48 h after the single oxygen exposure. The level of oxidation was evaluated by the rate of reactive oxygen species (ROS) and the levels of isoprostane. Antioxidant reactions were observed by total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT). The inflammatory response was measured using interleukin-6 (IL-6), neopterin, creatinine, and urates. Oxidation markers increased from 30 min on to reach a peak at 8 h. From 8 h post intake, the markers of inflammation took over, and more significantly with 100% than with 30%. This study suggests a biphasic response over time characterized by an initial “permissive oxidation” followed by increased inflammation. The antioxidant protection system seems not to be the leading actor in the first place. The kinetics of enzymatic reactions need to be better studied to establish therapeutic, training, or rehabilitation protocols aiming at a more targeted use of oxygen. Full article

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18 pages, 4928 KiB

Open AccessArticle

Proteomic Analysis Reveals That Mitochondria Dominate the Hippocampal Hypoxic Response in Mice

by Qianqian Shao, Jia Liu, Gaifen Li, Yakun Gu, Mengyuan Guo, Yuying Guan, Zhengming Tian, Wei Ma, Chaoyu Wang and Xunming Ji

Int. J. Mol. Sci. 2022, 23(22), 14094; https://doi.org/10.3390/ijms232214094 - 15 Nov 2022

Cited by 2 | Viewed by 1319

Abstract

Hypoxic stress occurs in various physiological and pathological states, such as aging, disease, or high-altitude exposure, all of which pose a challenge to many organs in the body, necessitating adaptation. However, the exact mechanisms by which hypoxia affects advanced brain function (learning and memory skills in particular) remain unclear. In this study, we investigated the effects of hypoxic stress on hippocampal function. Specifically, we studied the effects of the dysfunction of mitochondrial oxidative phosphorylation using global proteomics. First, we found that hypoxic stress impaired cognitive and motor abilities, whereas it caused no substantial changes in the brain morphology or structure of mice. Second, bioinformatics analysis indicated that hypoxia affected the expression of 516 proteins, of which 71.1% were upregulated and 28.5% were downregulated. We demonstrated that mitochondrial function was altered and manifested as a decrease in NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 expression, accompanied by increased reactive oxygen species generation, resulting in further neuronal injury. These results may provide some new insights into how hypoxic stress alters hippocampal function via the dysfunction of mitochondrial oxidative phosphorylation. Full article

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15 pages, 3528 KiB

Open AccessArticle

Varying Oxygen Partial Pressure Elicits Blood-Borne Microparticles Expressing Different Cell-Specific Proteins—Toward a Targeted Use of Oxygen?

by Costantino Balestra, Awadhesh K. Arya, Clément Leveque, Fabio Virgili, Peter Germonpré, Kate Lambrechts, Pierre Lafère and Stephen R. Thom

Int. J. Mol. Sci. 2022, 23(14), 7888; https://doi.org/10.3390/ijms23147888 - 17 Jul 2022

Cited by 17 | Viewed by 2463

Abstract

Oxygen is a powerful trigger for cellular reactions, but there are few comparative investigations assessing the effects over a large range of partial pressures. We investigated a metabolic response to single exposures to either normobaric (10%, 15%, 30%, 100%) or hyperbaric (1.4 ATA, 2.5 ATA) oxygen. Forty-eight healthy subjects (32 males/16 females; age: 43.7 ± 13.4 years, height: 172.7 ± 10.07 cm; weight 68.4 ± 15.7 kg) were randomly assigned, and blood samples were taken before and 2 h after each exposure. Microparticles (MPs) expressing proteins specific to different cells were analyzed, including platelets (CD41), neutrophils (CD66b), endothelial cells (CD146), and microglia (TMEM). Phalloidin binding and thrombospondin-1 (TSP), which are related to neutrophil and platelet activation, respectively, were also analyzed. The responses were found to be different and sometimes opposite. Significant elevations were identified for MPs expressing CD41, CD66b, TMEM, and phalloidin binding in all conditions but for 1.4 ATA, which elicited significant decreases. Few changes were found for CD146 and TSP. Regarding OPB, further investigation is needed to fully understand the future applications of such findings. Full article

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Review

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16 pages, 1239 KiB

Open AccessReview

The Normobaric Oxygen Paradox—Hyperoxic Hypoxic Paradox: A Novel Expedient Strategy in Hematopoiesis Clinical Issues

by Michele Salvagno, Giacomo Coppalini, Fabio Silvio Taccone, Giacomo Strapazzon, Simona Mrakic-Sposta, Monica Rocco, Maher Khalife and Costantino Balestra

Int. J. Mol. Sci. 2023, 24(1), 82; https://doi.org/10.3390/ijms24010082 - 21 Dec 2022

Cited by 9 | Viewed by 3343

Abstract

Hypoxia, even at non-lethal levels, is one of the most stressful events for all aerobic organisms as it significantly affects a wide spectrum of physiological functions and energy production. Aerobic organisms activate countless molecular responses directed to respond at cellular, tissue, organ, and whole-body levels to cope with oxygen shortage allowing survival, including enhanced neo-angiogenesis and systemic oxygen delivery. The benefits of hypoxia may be evoked without its detrimental consequences by exploiting the so-called normobaric oxygen paradox. The intermittent shift between hyperoxic-normoxic exposure, in addition to being safe and feasible, has been shown to enhance erythropoietin production and raise hemoglobin levels with numerous different potential applications in many fields of therapy as a new strategy for surgical preconditioning aimed at frail patients and prevention of postoperative anemia. This narrative review summarizes the physiological processes behind the proposed normobaric oxygen paradox, focusing on the latest scientific evidence and the potential applications for this strategy. Future possibilities for hyperoxic-normoxic exposure therapy include implementation as a synergistic strategy to improve a patient’s pre-surgical condition, a stimulating treatment in critically ill patients, preconditioning of athletes during physical preparation, and, in combination with surgery and conventional chemotherapy, to improve patients’ outcomes and quality of life. Full article

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14 pages, 715 KiB

Open AccessReview

Kidney Injuries and Evolution of Chronic Kidney Diseases Due to Neonatal Hyperoxia Exposure Based on Animal Studies

by Liang-Ti Huang and Chung-Ming Chen

Int. J. Mol. Sci. 2022, 23(15), 8492; https://doi.org/10.3390/ijms23158492 - 31 Jul 2022

Cited by 2 | Viewed by 1904

Abstract

Preterm birth interrupts the development and maturation of the kidneys during the critical growth period. The kidneys can also exhibit structural defects and functional impairment due to hyperoxia, as demonstrated by various animal studies. Furthermore, hyperoxia during nephrogenesis impairs renal tubular development and induces glomerular and tubular injuries, which manifest as renal corpuscle enlargement, renal tubular necrosis, interstitial inflammation, and kidney fibrosis. Preterm birth along with hyperoxia exposure induces a pathological predisposition to chronic kidney disease. Hyperoxia-induced kidney injuries are influenced by several molecular factors, including hypoxia-inducible factor-1α and interleukin-6/Smad2/transforming growth factor-β, and Wnt/β-catenin signaling pathways; these are key to cell proliferation, tissue inflammation, and cell membrane repair. Hyperoxia-induced oxidative stress is characterized by the attenuation or the induction of multiple molecular factors associated with kidney damage. This review focuses on the molecular pathways involved in the pathogenesis of hyperoxia-induced kidney injuries to establish a framework for potential interventions. Full article

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