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The relation of hyperbaric oxygen with oxidative stress - reactive molecules in action
Abstract
It is obvious that hyperbaric oxygen (HBO) administrations result in increased levels of oxidation products and a wide array of studies exist in literature reporting significant lipid peroxidation and/or protein oxidation in blood and tissues of HBO-exposed organisms. Nevertheless, in cases not exceeding the universally approved limits of this precious therapeutic modality, effective endogenous antioxidant defense mechanisms are present hindering a real state of “oxidative stress.” In early 2000s, hyperoxia achieved by HBO treatments has been reported to act in a double-faceted manner: (i) The hyperoxic effect which delivers oxygen to tissues with increased demand, and (ii) the reactive oxygen species (ROS)-mediated pathways known to be significantly elevated during HBO administrations. To date, ROS-signaling exhibits a great area in medical science opening new doors for researchers day by day. With regard to HBO, increased production of the superoxide radical followed by hydrogen peroxide seems to be the key point for its effects; the transcription factors nuclear factor erythroid 2-related factor 2 and hypoxia-inducible factor-1 alpha along with their main target protein heme oxygenase-1 are also involved in several mechanisms. This paper aims to briefly review some of the known interactions of HBO-triggered molecular details. By this way, we hope to attract more attention to this interesting research area in order to provide scientists a view for future projects.
... The initial uses of HBOT were based on the pressuredependent effervescent reducing action (Boyle-Marriott law) and the hyperoxygenation of tissues [17]. Pathologies with known benefits from the hyperoxic state created by HBOT are necrotizing tissues, radiation injury, wounds and burns, compartment syndromes, and gas gangrene [18], and several others as listed by the Undersea and Hyperbaric Medical Society [19]. ...
... Hyperbaric oxygen supplies the tissue with oxygen by enhancing its dissolution in the plasma, and by freeing hemoglobin from carbon monoxide [20]. Noteworthy, for certain conditions, HBOT is used as an adjunctive treatment and has demonstrated improvements in a variety of inflammatory or infectious disease models such as colitis, sepsis, and others [17]. Based on the anti-inflammatory and oxygenation mechanisms of HBOT, there is some potential for it to be a therapy used in neurodegenerative diseases, which we will discuss further below. ...
... It is important to note that the use of hyperbaric oxygen therapy must not exceed a pressure of 3 ATA and not be administered for more than 2 h at a time, as this typically results in toxicity [17]. The side effects of HBOT are usually dependent on pressure and time exposure [12]. ...
The World Health Organization estimates that by the year 2040, neurodegenerative diseases will be the second leading cause of death in developed countries, overtaking cancer-related deaths and exceeded only by cardiovascular disease–related death. The search for interventions has therefore become paramount to alleviate some of this burden. Based on pathways affected in neurodegenerative diseases, hyperbaric oxygen treatment (HBOT) could be a good candidate. This therapy has been used for the past 50 years for conditions such as decompression sickness and wound healing and has been shown to have promising effects in conditions associated with neurodegeneration and functional impairments. The goal of this review was to explore the history of hyperbaric oxygen therapy, its uses, and benefits, and to evaluate its effectiveness as an intervention in treating neurodegenerative diseases. Additionally, we examined common mechanisms underlying the effects of HBOT in different neurodegenerative diseases, with a special emphasis on epigenetics.
... 24 While the precise mechanisms are not yet fully understood, laboratory evidence suggests that HBOT temporarily inhibits neutrophils adhesion to endothelial cells via beta 2 integrin, which in turn decreases the ROS produced by neutrophils sequestered in the endothelium. 24,25 HBOT also leads to production of anti-inflammatory proteins and antioxidants enzymes. 24,25 Promising clinical studies have emerged suggesting HBOT's efficacy for reducing some postoperative complications, including following coronary artery bypass grafting. ...
... 24,25 HBOT also leads to production of anti-inflammatory proteins and antioxidants enzymes. 24,25 Promising clinical studies have emerged suggesting HBOT's efficacy for reducing some postoperative complications, including following coronary artery bypass grafting. 26,27 Notwithstanding, the effectiveness (if any) of HBOT across a range of procedures and postoperative outcomes has yet to be clearly quantified. ...
Background:
A primary underlying cause of postoperative complications is related to the surgical stress response, which may be mitigated by hyperbaric oxygen therapy (HBOT), the intermittent administration of oxygen at a pressure higher than the atmospheric pressure at sea level. Promising clinical studies have emerged suggesting HBOT's efficacy for reducing some postoperative complications. Notwithstanding, the effectiveness (if any) of HBOT across a range of procedures and postoperative outcomes has yet to be clearly quantified.
Objective:
This systematic review aimed to summarise the existing literature on peri-operative HBOT to investigate its potential to optimise surgical patient outcome.
Design:
A systematic review of randomised controlled trials (RCTs) with narrative summary of results.
Data sources:
MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials were searched without language restrictions through to 19 June 2018.
Eligibility criteria:
Studies were included if they involved patients of any age undergoing any surgical procedure and provided with at least one HBOT session in the peri-operative period. Two independent reviewers screened the initial identified trials and determined those to be included. Risk of bias was assessed using the Cochrane Risk of Bias tool for RCTs.
Results:
The search retrieved 775 references, of which 13 RCTs were included (627 patients). Ten RCTs (546 patients) reported treatment was effective for improving at least one of the patient outcomes assessed, while two studies (55 patients) did not find any benefit and one study (26 patients) found a negative effect. A wide range of patient outcomes were reported, and several other methodological limitations were observed among the included studies, such as limited use of sham comparator and lack of blinding.
Conclusion:
Peri-operative preventive HBOT may be a promising intervention to improve surgical patient outcome. However, future work should consider addressing the methodological weaknesses identified in this review.
Trial registration:
The protocol (CRD42018102737) was registered with the International ProspectiveRegister of Systematic Reviews (PROSPERO).
... One of the proposed mechanisms affecting vascular function is the modulation of the endothelium-dependent vasodilation (16,17). The final effect of HBO importantly depends on the amount, that is, the pressure applied, and the time of exposure, as well as the mode of application (i.e., continuous vs. intermittent) (45,61,62). On a longer term, HBO has been shown to induce expression of various growth factors, stimulate angiogenesis, and affect endothelial cell adhesion molecule expression (16,71). ...
Šet, V, and Lenasi, H. Does hyperbaric oxygenation improve athletic performance? J Strength Cond Res XX(X): 000-000, 2022-Hyperbaric oxygen (HBO) has been suggested to affect oxygen availability and performance, and delay the onset of fatigue. Many mechanisms of HBO-induced alterations have been proposed, including modulation of various metabolic pathways, and the antioxidant defense mechanisms. As exercise per se affects similar aspects, it is tempting to speculate that simultaneous application of both, exercise and HBO might have synergistic effects. The aim of this review was to search through the currently available literature and evaluate the effect of acute exposure to HBO on exercise performance, potential effects of a combination of HBO and physical training, and to elucidate some possible mechanisms behind. We conducted searches in the PubMed and Scopus databases (search term: "hyperbaric" AND "oxygen" AND "exercise") and in relevant hyperbaric textbook and assessed potentially eligible full texts for details. Meta-analysis could not be performed because of a few available and rather heterogeneous studies. Twenty-seven studies were included in the final assessment (14 on exercise during HBO, 9 on exercise following HBO, 4 on applying HBO during recovery and rest between exercise bouts, and 3 on a combination of HBO and training). The results are contradictory, showing either positive or none ergogenic effects. There is some risk of bias and placebo effect. Discrepant findings of the available studies might partly be explained by different protocols applied, both regarding HBO and exercise intensity and regimen. There is a need for further research with well-designed trials to evaluate the effect of HBO on performance before recommending it to routine use in athletes.
... One of the proposed mechanisms affecting vascular function is the modulation of the endothelium-dependent vasodilation (16,17). The final effect of HBO importantly depends on the amount, that is, the pressure applied, and the time of exposure, as well as the mode of application (i.e., continuous vs. intermittent) (45,61,62). On a longer term, HBO has been shown to induce expression of various growth factors, stimulate angiogenesis, and affect endothelial cell adhesion molecule expression (16,71). ...
Šet, V, and Lenasi, H. Does hyperbaric oxygenation improve athletic performance? J Strength Cond Res XX(X): 000-000, 2022-Hyperbaric oxygen (HBO) has been suggested to affect oxygen availability and performance, and delay the onset of fatigue. Many mechanisms of HBO-induced alterations have been proposed, including modulation of various metabolic pathways, and the antioxidant defense mechanisms. As exercise per se affects similar aspects, it is tempting to speculate that simultaneous application of both, exercise and HBO might have synergistic effects. The aim of this review was to search through the currently available literature and evaluate the effect of acute exposure to HBO on exercise performance, potential effects of a combination of HBO and physical training, and to elucidate some possible mechanisms behind. We conducted searches in the PubMed and Scopus databases (search term: "hyperbaric" AND "oxygen" AND "exercise") and in relevant hyperbaric textbook and assessed potentially eligible full texts for details. Meta-analysis could not be performed because of a few available and rather heterogeneous studies. Twenty-seven studies were included in the final assessment (14 on exercise during HBO, 9 on exercise following HBO, 4 on applying HBO during recovery and rest between exercise bouts, and 3 on a combination of HBO and training). The results are contradictory, showing either positive or none ergogenic effects. There is some risk of bias and placebo effect. Discrepant findings of the available studies might partly be explained by different protocols applied, both regarding HBO and exercise intensity and regimen. There is a need for further research with well-designed trials to evaluate the effect of HBO on performance before recommending it to routine use in athletes.
... 17 HBO therapy with a period of relative hypoxia provides an important oxygen gradient needed to stimulate angiogenesis, fibroblast proliferation, collagen formation, and leukocyte activation which is necessary for tissue repair. 18 HBOT is reported to improve neurologic recovery after bone marrow injury by ameliorating mitochondrial dysfunction in the motor cortex and bone marrow, arresting the spread of bleeding, reversing the hypoxic process, and reducing edema. 19 Patel et al who collected various data on HBOT in bone marrow injury, suggested 6 action mechanisms. ...
We reported a rare case demonstrating that the hyperbaric oxygen chamber provided faster clinical improvement in a patient with a variant of Guillain-Barre Syndrome (GBS). A patient with progressive, acute weakness of upper extremity locomotor muscles and with difficulty breathing and swallowing was diagnosed with axonal GBS. Despite life-saving conventional therapies, there was no significant improvement until day 5. During hyperbaric oxygen therapy, there were daily gradual improvements until day 20, at which time the patient was capable of walking slowly without using a walking aid.
... In our study, HO-1 expression was only mildly increased in AKI + HBO normotensive Wistar rats, probably due to previous compensatory increasing after AKI induction. HO-1, also called heat shock protein (HSP)32 is the first molecular which is reported to be a mediator for achieved improvement induced by HBO, particularly by increasing the tolerance of the organism against oxidative damage [40]. Rothfuss et al. demonstrated involvement of HO-1 in the adaptive protection of human lymphocytes after hyperbaric oxygen treatment [41]. ...
Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.
... 9 HBOT is a well-established and safe 10 method to increase tissue oxygen delivery up to 10-fold at 2 ATA pressure. [11][12][13] Hyper-oxygenation of arterial blood with plasma-dissolved oxygen through HBOT has a strong anti-inflammatory [13][14][15][16] effect and may have a direct viricidal effect on SARS-CoV-2. HBOT is currently approved by the Undersea and Hyperbaric Medical Society and regulatory agencies (e.g., Health Canada, Food and Drug Administration), for 14 indications, including both elective (e.g., soft tissue radiation therapy complications, non-healing chronic wounds) and urgent conditions (e.g., carbon monoxide poisoning, decompression sickness, gas embolism). ...
Background: At least 1 in 6 COVID-19 patients admitted to hospital and receiving supplemental oxygen will die of complications. More than 50% of patients with COVID-19 that receive invasive treatment such as mechanical ventilation will die in hospital. Such impacts overwhelm the limited intensive care unit resources and may lead to further deaths given inadequate access to care.
Hyperbaric oxygen therapy (HBOT) is defined as breathing 100% oxygen at a pressure higher than 1.4 atmosphere absolute (ATA). HBOT is safe, including for lungs, when administered by experienced teams and is routinely administrated for a number of approved indications. Preliminary clinical evidence suggests clinical improvement when hypoxemic COVID-19 patients are treated with HBOT.
Objective: We aim to determine the effectiveness of HBOT for improving oxygenation, morbidity, and mortality among hypoxemic COVID-19 patients.
Methods and analysis: This trial is a sequential Bayesian Parallel-group, individually Randomized, Open, Blinded Endpoint controlled trial. Admitted hypoxemic COVID-19 patients who require supplemental oxygen (without high flow and mechanical ventilation) to maintain a satisfying tissue oxygenation will be eligible to participate. The anticipated sample size of 234 patients is informed by data from a treatment trial of COVID patients recently published. The intervention group will receive one HBOT per day at 2.0 ATA for 75 minutes. Daily HBOT will be administered until either the patient does not require any oxygen supplementation or requires any type of mechanical ventilation or high flow oxygenation until day 28 post-randomization. Patients in the control group will receive the current standard of care treatment (no HBOT). The primary outcome of this trial will be the 7-level COVID ordinal outcomes scale assessed on Day 7 post-randomization. Secondary outcomes will include: (a) clinical outcomes (length of hospital stay, days with oxygen supplementation, oxygen flow values to obtain a saturation by pulse oximetry ≥90%, intensive care admission and length of stay, days on invasive mechanical ventilation or high flow oxygen, sleep quality, fatigue, major thrombotic events, the 7-level COVID ordinal outcomes scale on Day 28; mortality, safety); (b) biological outcomes (plasma inflammatory markers); and (c) health system outcomes (cost of care and cost-effectiveness). Predetermined inclusion/exclusion criteria have been specified. The analytical approach for the primary outcome will use a Bayesian proportional odds ordinal logistic semiparametric model. The primary analysis will be by intention-to-treat. Bayesian posterior probabilities will be calculated every 20 patients to assess accumulating evidence for benefit or harm. A planned subgroup analysis will be performed for pre-specified variables known to impact COVID-19 prognosis and/or HBOT (biologic sex and age).
Discussion: Based on the mortality rate and substantial burden of COVID-19 on the healthcare system, it is imperative that solutions be found. HBOT is a non-invasive and low-risk intervention when contraindications are respected. The established safety and relatively low cost of providing HBOT along with its potential to improve the prognosis of severe COVID-19 patients make this intervention worth studying, despite the current limited number of HBOT centres. If this trial finds that HBOT significantly improves outcome and prevents further deterioration leading to critical care for severe COVID-19 patients, practice will change internationally. If no benefit is found from the intervention, then the current standard of care (no HBOT) will be supported by level I evidence.
Treatment of Alzheimer’s disease (AD) has been limited to managing of symptoms or anti-amyloid therapy with limited results and uncertainty. Seeking out new therapies that can reverse the effects of this devastating disease is important. Hyperbaric oxygen (HBO) therapy could be such a candidate as it has been shown to improve brain function in certain neurological conditions. Furthermore, the role sex plays in the vulnerability/resilience to AD remains equivocal. An understanding of what makes one sex more vulnerable to AD could unveil new pathways for therapy development. In this study, we investigated the effects of HBO on cognitive, motor, and affective function in a mouse model of AD (5xFAD) and assessed protein oxidation in peripheral tissues as a safety indicator. The motor and cognitive abilities of 5xFAD mice were significantly impaired. HBO therapy improved cognitive flexibility and associative learning of 5xFAD females but not males, but HBO had no effect other aspects of cognition. HBO also reversed AD-related declines in balance but had no impact on gait and anxiety-like behavior. HBO did not affect body weights or oxidative stress in peripheral tissues. Our study provides further support for HBO therapy as a potential treatment for AD and emphasizes the importance of considering sex as a biological variable in therapeutic development. Further investigations into the underlying mechanisms of HBO’s sex-specific responses are warranted, as well as optimizing treatment protocols for maximum benefits.
Oxidative stress has been considered as a central aggravating factor in the development of postischemic acute kidney injury (AKI). The aim of this study was to perform the immunohistochemical analysis of 4-hydroxynonenal (4-HNE), neutrophil gelatinase-associated lipocalin (NGAL), and heme oxygenase-1 (HO-1) tissue expression after apocynin (APO) treatment and hyperbaric oxygenation (HBO) preconditioning, applied as single or combined protocol, in postischemic acute kidney injury induced in spontaneously hypertensive rats (SHR). Twenty-four hours before AKI induction, HBO preconditioning was carried out by exposing to pure oxygen (2.026 bar) twice a day, for 60 min in two consecutive days. Acute kidney injury was induced by removal of the right kidney while the left renal artery was occluded for 45 min by atraumatic clamp. Apocynin was applied in a dose of 40 mg/kg body weight, intravenously, 5 min before reperfusion. We showed increased 4-HNE renal expression in postischemic AKI compared to Sham-operated (SHAM) group. Apocynin treatment, with or without HBO preconditioning, improved creatinine and phosphate clearances, in postischemic AKI. This improvement in renal function was accompanied with decreased 4-HNE, while HO-1 kidney expression restored close to the control group level. NGAL renal expression was also decreased after apocynin treatment, and HBO preconditioning, with or without APO treatment. Considering our results, we can say that 4-HNE tissue expression can be used as a marker of oxidative stress in postischemic AKI. On the other hand, apocynin treatment and HBO preconditioning reduced oxidative damage, and this protective effect might be expected even in experimental hypertensive condition.
Background/aim:
Hyperbaric oxygen therapy (HBOT) causes insulin sensitivity, but the reason for this is not yet known. The aim of the present study was to investigate the effect of HBOT on insulin sensitivity via resistin, plasminogen activator inhibitor-I (PAI-I), and adiponectin.
Material and methods:
The study was designed using HBOT and control groups, with eight rats in each group. After 20 days of HBOT under 2.5 atmospheres for 90 minutes, the fasting insulin (FI), resistin, PAI-I, homeostatic model assessment of insulin resistance scores (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose (FPG), triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the plasma were measured. The resistin, PAI-I, and adiponectin mRNA expression levels were also measured in the adipose tissue.
Results:
Compared to the control group, the FI, FPG, and HOMA-IR scores were significantly lower in the HBOT group, whereas the HDL-C and QUICKI scores were found to be higher. In addition, the resistin, adiponectin, and PAI-I mRNA expression levels were also higher in the HBOT group.
Conclusions:
The present study demonstrated that the HBOT had regulated the FI, FPG, and HDL-C associated with metabolic syndrome and diabetes mellitus. Moreover, the study showed that HBOT causes insulin sensitivity by raising adiponectin.
With the rise of the burden of ischemic heart disease, both clinical and economic evidence show a desperate need to protect the heart against myocardium ischemia-reperfusion injury-related complications following cardiac surgery or percutaneous coronary intervention. However, there is no effective intervention for myocardium ischemia-reperfusion injury as yet.
We pretreated mice with 4 daily 2.0 absolute atmosphere (ATA) hyperbaric oxygen, then observed its effects on heart function parameters and infarct size following in situ ischemia-reperfusion. Multiple oxidative and inflammation products were measured in the myocardium. Next, we investigated the expression of heme oxygenase 1 (HO-1), phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt) pathway, and NF-E2-related factor 2 (Nrf2) in the presence of myocardium ischemia-reperfusion injury, hyperbaric oxygen preconditioning, and their inhibitors and their effects on heart function parameters.
Hyperbaric oxygen preconditioning ameliorated the cardiac function and histological alterations induced by myocardium ischemia-reperfusion injury, decreased oxidative products and proinflammatory cytokine. Hyperbaric oxygen preconditioning increased expression of HO-1, which was suppressed by PI3K inhibitor LY294002, Nrf2 knockout, and Akt inhibitor triciribine. The expression of Nrf2 was enhanced by hyperbaric oxygen preconditioning, but decreased by LY294002 and triciribine. The Akt was also activated by hyperbaric oxygen preconditioning but suppressed by LY294002. The hemodynamic assays showed that cardiac function was suppressed by LY294002, Nrf2 knockout, and triciribine.
These data present a novel signaling mechanism by which hyperbaric oxygen preconditioning protects myocardium ischemia-reperfusion injury via PI3K/Akt/Nrf2-dependent antioxidant defensive system.
© The Author(s) 2015.
Hyperbaric oxygen (HBO) therapy has been used as an adjunctive therapy for diabetic foot ulcers, although its mechanism of action is not completely understood. Recently, it has been shown that HBO mobilizes the endothelial progenitor cells (EPCs) from bone marrow that eventually will aggregate in the wound. However, the gathering of the EPCs in diabetic wounds is impaired due to the decreased levels of local stromal-derived factor-1α (SDF-1α). Therefore, we investigated the influence of HBO on HIF-1, which is a central regulator of SDF-1α and is down-regulated in diabetic wounds. The effects of HBO on HIF-1α function were studied in human dermal fibroblasts, SKRC7 cells and HIF-1α knock-out and wild-type mouse embryonic fibroblasts using appropriate techniques (Western blot, Quantitative-PCR and Luciferase hypoxia-responsive element (HRE) reporter assay). Cellular proliferation was assessed using H3-thymidine incorporation assay. The effect of HIF in combination with HBOT was tested by inoculating stable HIF-1α-expressing adenovirus (Adv-HIF) into experimental wounds in db/db mice exposed to HBO.HBO activates HIF-1α at several levels by increasing both HIF-1α stability (by a non-canonical mechanism) and activity (as show both by induction of relevant target-genes and by a specific reporter assay). HIF-1α induction has important biological relevance because the induction of fibroblast proliferation in HBO disappears when HIF-1α is knocked down. Moreover, the local transfer of stable HIF-1α-expressing adenovirus (Adv-HIF) into experimental wounds in diabetic (db/db mice) has an additive effect on HBO-mediated improvements in wound healing.In conclusion HBO stabilizes and activates HIF-1, which contributes to increased cellular proliferation. In diabetic animals, the local transfer of active HIF further improves the effects of HBO on wound healing.
The antioxidant enzyme superoxide dismutase (SOD) found in the cytosol of eucaryotic cells and the plasma protein ceruloplasmin are copper containing proteins thought to be important in providing protection from oxygen toxicity. To investigate the hypothesis that copper deficiency in the rat could result in decreased lung SOD activity and plasma ceruloplasmin concentration resulting in increased susceptibility to O2 lung damage, we performed a series of experiments exposing copper-deficient and control rats to normobaric and hyperbaric hyperoxia. Lung SOD activity in the copper-deficient rats was found to be 56% of control and ceruloplasmin content was 6% of control. The copper-deficient rats exhibited increased mortality and enhanced pulmonary toxicity as evidenced by increased pathologic damage and lung edema during the normobaric exposure to 85% O2. Copper-deficient animals also showed increased susceptibility to a hyperbaric exposure of 4 ata of 100% O2 with a decreased time of survival. The copper-deficient rat represents a new model for the study of oxidant injury.
Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. Pervious studies have shown hyperbaric oxygen preconditioning (HBO-PC) had a protective effect on oxidative injury. In the present study, we investigated the effect of HBO-PC on HALI in rats. The results demonstrated that HBO-PC ameliorated the lung biochemical and histological alterations induced by hyperoxia, decreased oxidative products but increased antioxidant enzymes. Furthermore, HBO-PC up-regulated heme oxygenase-1 (HO-1) mRNA and activity in lung tissues. The administration of HO-1 inhibitor, Zinc protoporphyrin IX, abolished its protective effects. The data showed that HBO-PC could protect rats against HALI and the anti-oxidative effect may be related to the up-regulation of HO-1.
Background:
The primary goal of this study was to test whether high-altitude exposure (HAE of 9.7% O2 at 0.47 absolute atmosphere [ATA] for 3 days) was capable of increasing lung edema, neutrophil, and hemorrhage scores as well as decreasing lung levels of both aquaporin 1 (AQP1) and AQP5 proteins and messenger RNA (mRNA) expression in rats, with a secondary goal to test whether a preinduction of heat shock protein 70 (HSP70) by hyperbaric oxygen preconditioning (HBO2P of 100% O2 at 2.0 ATA for 1 hour per day for 5 consecutive days) attenuated the HAE-induced increased lung injury scores and decreased lung AQP1 and AQP5 protein and mRNA expressions.
Methods:
Rats were assigned to (1) non-HBO2P (21% O2 at 1.0 ATA) + non-HAE (21% O2 at 1.0 ATA) group; (2) non-HBO2P + HAE group; (3) HBO2P + HAE group; and HBO2P + HSP70 antibodies (Ab) + HAE group. For the HSP70 Ab group, a neutralizing HSP70 Ab was injected intravenously at 24 hours before HAE. All the physiologic and biochemical parameters were obtained at the end of HAE or the equivalent period of non-HAE. The cardiovascular and blood gas parameters were monitored for all experiments. Bronchoalveolar lavage (BAL) was performed to determine proinflammatory cytokines (interleukin 6, interleukin 1β, and tumor necrosis factor α). Parts of the lung were excised for myeloperoxidase activity measurement, whereas the rest was collected for lung damage score assessments. AQP1 and AQP5 protein and mRAN expressions were also determined in the lung tissues.
Results:
In the non-HBO2P + HAE group, the animals displayed higher values of lung myeloperoxidase activity, BAL proinflammatory cytokines, lung water weight, and acute lung injury scores compared with those of the non-HBO2P + non-HAE controls. In contrast, the non-HBO2P + HAE group rats had lower values of lung AQP1 and AQP5 protein and mRNA expressions, mean arterial pressure, heart rate, SO2, Paco2, HCO3, and pH compared with those of non-HBO2P + non-HAE group rats. The increased acute lung edema, neutrophil, and hemorrhage scores; increased BAL levels of proinflammatory cytokines; decreased lung AQP1 and AQP5 protein and mRNA expressions; and hypotension, bradycardia, hypoxia, and acidosis caused by HAE were all significantly attenuated by HBO2P.
Conclusion:
Our data indicate that HBO2P may attenuate high-altitude acute lung injury by a preinduction of lung HSP70 in rats.
Exposure to hyperbaric oxygen (HBO2) before a crucial event, with the plan to create a preventing therapeutic situation, has been defined "preconditioning" and is emerging as a useful adjunct both in diving medicine as well before ischemic or inflammatory events. Oxygen pre-breathing before diving has been extensively documented in recreational, technical, commercial and military diving for tissue denitrogenation, resulting in reduced post-diving bubble loads, reduced decompression requirements and more rapid return to normal platelet function after a decompression. Preoxygenation at high atmospheric pressure has also been used in patients before exposure to clinical situations with beneficial effects, but the mechanisms of action have not yet been ascertained. During the reperfusion of ischemic tissue, oxygenated blood increases numbers and activities of oxidants generated in tissues. Previous reports showed that HBO2 preconditioning caused the activation of antioxidative enzymes and related genes in the central nervous system, including catalase (CAT), superoxide dismutase and heme oxygenase-1. Despite the increasing number of basic science publications on this issue, studies describing HBO2 preconditioning in the clinical practice remain scarce. To date, only a few studies have investigated the preconditioning effects of HBO2 in relation to the human brain and myocardium with robust and promising results.