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Oxygen Variations, 2nd Edition
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Oxygen Variations, 2nd Edition

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: 20 March 2025 | Viewed by 13439

Special Issue Editors

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. 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
Dr. Gerardo Bosco

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Guest Editor
Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
Interests: environmental physiology; hyperbaric oxygen treatment; hyperoxia; oxidative stress; diving physiology; hypoxia
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 achieving steady states. Understandably, this was a clear need, as we wanted to reassure ourselves of the validity of measurements and the stability of the assessments being 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 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 current and future research can focus on changes, or unsteady states.

We want to look to the future with this new Special Issue of the International Journal of Molecular Sciences within the Biochemistry & Molecular Biology section, particularly focusing 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 or 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 regarding these topics will be welcomed.

Prof. Dr. Costantino Balestra
Prof. Dr. Simona Mrakic-Sposta
Dr. Gerardo Bosco
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
  • gene expression
  • adaptive reactions
  • extreme environments

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Related Special Issue

Published Papers (6 papers)

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Research

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15 pages, 3502 KiB  
Article
The Effect of Targeted Hyperoxemia on Brain Immunohistochemistry after Long-Term, Resuscitated Porcine Acute Subdural Hematoma and Hemorrhagic Shock
by Franziska Münz, Thomas Datzmann, Andrea Hoffmann, Michael Gröger, René Mathieu, Simon Mayer, Fabian Zink, Holger Gässler, Eva-Maria Wolfschmitt, Melanie Hogg, Enrico Calzia, Pierre Asfar, Peter Radermacher, Thomas Kapapa and Tamara Merz
Int. J. Mol. Sci. 2024, 25(12), 6574; https://doi.org/10.3390/ijms25126574 - 14 Jun 2024
Cited by 1 | Viewed by 810
Abstract
Epidemiological data suggest that moderate hyperoxemia may be associated with an improved outcome after traumatic brain injury. In a prospective, randomized investigation of long-term, resuscitated acute subdural hematoma plus hemorrhagic shock (ASDH + HS) in 14 adult, human-sized pigs, targeted hyperoxemia (200 < [...] Read more.
Epidemiological data suggest that moderate hyperoxemia may be associated with an improved outcome after traumatic brain injury. In a prospective, randomized investigation of long-term, resuscitated acute subdural hematoma plus hemorrhagic shock (ASDH + HS) in 14 adult, human-sized pigs, targeted hyperoxemia (200 < PaO2 < 250 mmHg vs. normoxemia 80 < PaO2 < 120 mmHg) coincided with improved neurological function. Since brain perfusion, oxygenation and metabolism did not differ, this post hoc study analyzed the available material for the effects of targeted hyperoxemia on cerebral tissue markers of oxidative/nitrosative stress (nitrotyrosine expression), blood–brain barrier integrity (extravascular albumin accumulation) and fluid homeostasis (oxytocin, its receptor and the H2S-producing enzymes cystathionine-β-synthase and cystathionine-γ-lyase). After 2 h of ASDH + HS (0.1 mL/kgBW autologous blood injected into the subdural space and passive removal of 30% of the blood volume), animals were resuscitated for up to 53 h by re-transfusion of shed blood, noradrenaline infusion to maintain cerebral perfusion pressure at baseline levels and hyper-/normoxemia during the first 24 h. Immediate postmortem, bi-hemispheric (i.e., blood-injected and contra-lateral) prefrontal cortex specimens from the base of the sulci underwent immunohistochemistry (% positive tissue staining) analysis of oxidative/nitrosative stress, blood–brain barrier integrity and fluid homeostasis. None of these tissue markers explained any differences in hyperoxemia-related neurological function. Likewise, hyperoxemia exerted no deleterious effects. Full article
(This article belongs to the Special Issue Oxygen Variations, 2nd Edition)
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18 pages, 9005 KiB  
Article
Hyperbaric Oxygen Reduces Oxidative Stress Impairment and DNA Damage and Simultaneously Increases HIF-1α in Ischemia–Reperfusion Acute Kidney Injury
by Jelena Nesovic Ostojic, Sanjin Kovacevic, Milan Ivanov, Predrag Brkic, Maja Zivotic, Nevena Mihailovic-Stanojevic, Danijela Karanovic, Una Jovana Vajic, Rada Jeremic, Djurdjica Jovovic and Zoran Miloradovic
Int. J. Mol. Sci. 2024, 25(7), 3870; https://doi.org/10.3390/ijms25073870 - 30 Mar 2024
Cited by 3 | Viewed by 1384
Abstract
The central exacerbating factor in the pathophysiology of ischemic–reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a [...] Read more.
The central exacerbating factor in the pathophysiology of ischemic–reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the “master switch” for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats. Full article
(This article belongs to the Special Issue Oxygen Variations, 2nd Edition)
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19 pages, 1362 KiB  
Article
Exposure to Non-Steady-State Oxygen Is Reflected in Changes to Arterial Blood Gas Values, Prefrontal Cortical Activity, and Systemic Cytokine Levels
by Elizabeth G. Damato, Joseph S. Piktel, Seunghee P. Margevicius, Seth J. Fillioe, Lily K. Norton, Alireza Abdollahifar, Kingman P. Strohl, David S. Burch and Michael J. Decker
Int. J. Mol. Sci. 2024, 25(6), 3279; https://doi.org/10.3390/ijms25063279 - 14 Mar 2024
Viewed by 933
Abstract
Onboard oxygen-generating systems (OBOGSs) provide increased inspired oxygen (FiO2) to mitigate the risk of neurologic injury in high altitude aviators. OBOGSs can deliver highly variable oxygen concentrations oscillating around a predetermined FiO2 set point, even when [...] Read more.
Onboard oxygen-generating systems (OBOGSs) provide increased inspired oxygen (FiO2) to mitigate the risk of neurologic injury in high altitude aviators. OBOGSs can deliver highly variable oxygen concentrations oscillating around a predetermined FiO2 set point, even when the aircraft cabin altitude is relatively stable. Steady-state exposure to 100% FiO2 evokes neurovascular vasoconstriction, diminished cerebral perfusion, and altered electroencephalographic activity. Whether non-steady-state FiO2 exposure leads to similar outcomes is unknown. This study characterized the physiologic responses to steady-state and non-steady-state FiO2 during normobaric and hypobaric environmental pressures emulating cockpit pressures within tactical aircraft. The participants received an indwelling radial arterial catheter while exposed to steady-state or non-steady-state FiO2 levels oscillating ± 15% of prescribed set points in a hypobaric chamber. Steady-state exposure to 21% FiO2 during normobaria produced arterial blood gas values within the anticipated ranges. Exposure to non-steady-state FiO2 led to PaO2 levels higher upon cessation of non-steady-state FiO2 than when measured during steady-state exposure. This pattern was consistent across all FiO2 ranges, at each barometric condition. Prefrontal cortical activation during cognitive testing was lower following exposure to non-steady-state FiO2 >50% and <100% during both normobaria and hypobaria of 494 mmHg. The serum analyte levels (IL-6, IP-10, MCP-1, MDC, IL-15, and VEGF-D) increased 48 h following the exposures. We found non-steady-state FiO2 levels >50% reduced prefrontal cortical brain activation during the cognitive challenge, consistent with an evoked pattern of neurovascular constriction and dilation. Full article
(This article belongs to the Special Issue Oxygen Variations, 2nd Edition)
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Review

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19 pages, 1513 KiB  
Review
Oxy-Inflammation in Humans during Underwater Activities
by Alessandra Vezzoli, Simona Mrakic-Sposta, Andrea Brizzolari, Costantino Balestra, Enrico Maria Camporesi and Gerardo Bosco
Int. J. Mol. Sci. 2024, 25(5), 3060; https://doi.org/10.3390/ijms25053060 - 6 Mar 2024
Cited by 2 | Viewed by 3129
Abstract
Underwater activities are characterized by an imbalance between reactive oxygen/nitrogen species (RONS) and antioxidant mechanisms, which can be associated with an inflammatory response, depending on O2 availability. This review explores the oxidative stress mechanisms and related inflammation status (Oxy-Inflammation) in underwater activities [...] Read more.
Underwater activities are characterized by an imbalance between reactive oxygen/nitrogen species (RONS) and antioxidant mechanisms, which can be associated with an inflammatory response, depending on O2 availability. This review explores the oxidative stress mechanisms and related inflammation status (Oxy-Inflammation) in underwater activities such as breath-hold (BH) diving, Self-Contained Underwater Breathing Apparatus (SCUBA) and Closed-Circuit Rebreather (CCR) diving, and saturation diving. Divers are exposed to hypoxic and hyperoxic conditions, amplified by environmental conditions, hyperbaric pressure, cold water, different types of breathing gases, and air/non-air mixtures. The “diving response”, including physiological adaptation, cardiovascular stress, increased arterial blood pressure, peripheral vasoconstriction, altered blood gas values, and risk of bubble formation during decompression, are reported. Full article
(This article belongs to the Special Issue Oxygen Variations, 2nd Edition)
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25 pages, 2744 KiB  
Review
Oxidative Stress and Cerebral Vascular Tone: The Role of Reactive Oxygen and Nitrogen Species
by Michele Salvagno, Elda Diletta Sterchele, Mario Zaccarelli, Simona Mrakic-Sposta, Ian James Welsby, Costantino Balestra and Fabio Silvio Taccone
Int. J. Mol. Sci. 2024, 25(5), 3007; https://doi.org/10.3390/ijms25053007 - 5 Mar 2024
Cited by 4 | Viewed by 2653
Abstract
The brain’s unique characteristics make it exceptionally susceptible to oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) production, reactive nitrogen species (RNS) production, and antioxidant defense mechanisms. This review explores the factors contributing to the brain’s vascular tone’s vulnerability [...] Read more.
The brain’s unique characteristics make it exceptionally susceptible to oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) production, reactive nitrogen species (RNS) production, and antioxidant defense mechanisms. This review explores the factors contributing to the brain’s vascular tone’s vulnerability in the presence of oxidative damage, which can be of clinical interest in critically ill patients or those presenting acute brain injuries. The brain’s high metabolic rate and inefficient electron transport chain in mitochondria lead to significant ROS generation. Moreover, non-replicating neuronal cells and low repair capacity increase susceptibility to oxidative insult. ROS can influence cerebral vascular tone and permeability, potentially impacting cerebral autoregulation. Different ROS species, including superoxide and hydrogen peroxide, exhibit vasodilatory or vasoconstrictive effects on cerebral blood vessels. RNS, particularly NO and peroxynitrite, also exert vasoactive effects. This review further investigates the neuroprotective effects of antioxidants, including superoxide dismutase (SOD), vitamin C, vitamin E, and the glutathione redox system. Various studies suggest that these antioxidants could be used as adjunct therapies to protect the cerebral vascular tone under conditions of high oxidative stress. Nevertheless, more extensive research is required to comprehensively grasp the relationship between oxidative stress and cerebrovascular tone, and explore the potential benefits of antioxidants as adjunctive therapies in critical illnesses and acute brain injuries. Full article
(This article belongs to the Special Issue Oxygen Variations, 2nd Edition)
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12 pages, 648 KiB  
Review
Hyperoxia: Effective Mechanism of Hyperbaric Treatment at Mild-Pressure
by Mariana Cannellotto, Ali Yasells García and María Silvina Landa
Int. J. Mol. Sci. 2024, 25(2), 777; https://doi.org/10.3390/ijms25020777 - 8 Jan 2024
Cited by 2 | Viewed by 3769
Abstract
HBOT increases the proportion of dissolved oxygen in the blood, generating hyperoxia. This increased oxygen diffuses into the mitochondria, which consume the majority of inhaled oxygen and constitute the epicenter of HBOT effects. In this way, the oxygen entering the mitochondria can reverse [...] Read more.
HBOT increases the proportion of dissolved oxygen in the blood, generating hyperoxia. This increased oxygen diffuses into the mitochondria, which consume the majority of inhaled oxygen and constitute the epicenter of HBOT effects. In this way, the oxygen entering the mitochondria can reverse tissue hypoxia, activating the electron transport chain to generate energy. Furthermore, intermittent HBOT is sensed by the cell as relative hypoxia, inducing cellular responses such as the activation of the HIF-1α pathway, which in turn, activates numerous cellular processes, including angiogenesis and inflammation, among others. These effects are harnessed for the treatment of various pathologies. This review summarizes the evidence indicating that the use of medium-pressure HBOT generates hyperoxia and activates cellular pathways capable of producing the mentioned effects. The possibility of using medium-pressure HBOT as a direct or adjunctive treatment in different pathologies may yield benefits, potentially leading to transformative therapeutic advancements in the future. Full article
(This article belongs to the Special Issue Oxygen Variations, 2nd Edition)
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