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Hyperbaric Environment: Oxygen and Cellular Damage versus Protection

Angela M. Poff, Dawn Kernagis, Dominic P. D'Agostino

10.1002/cphy.c150032

Source: Volume 7, Issue 1, January 2017

Published online: December 2016

Full Article on Wiley Online Library



ABSTRACT

The elevation of tissue pO2 induced by hyperbaric oxygen (HBO) is a physiological stimulus that elicits a variety of cellular responses. These effects are largely mediated by, or in response to, an increase in the production of reactive oxygen and nitrogen species (RONS). The major consequences of elevated RONS include increased oxidative stress and enhanced antioxidant capacity, and modulation of redox‐sensitive cell signaling pathways. Interestingly, these phenomena underlie both the therapeutic and potentially toxic effects of HBO. Emerging evidence indicates that supporting mitochondrial health is a potential method of enhancing the therapeutic efficacy of, and preventing oxygen toxicity during, HBO. This review will focus on the cellular consequences of HBO, and explore how these processes mediate a delicate balance of cellular protection versus damage. © 2017 American Physiological Society. Compr Physiol 7:213‐234, 2017.

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Figure 1. Figure 1. Mitochondrial RONS production—OxS versus signaling. The mitochondrion is implicated in the generation of ROS and RNS. In most cells, the mitochondrial respiratory chain is recognized as the major site of RONS production in the form of superoxide, hydrogen peroxide and the hydroxyl radical. These RONS are considered important for normal cell signaling. However, excessive amounts of RONS are deleterious for the cell, contributing to a variety of pathological processes. RONS production can result in the setup of a vicious cycle of oxidative damage causing a progressive alteration of mtDNA and mitochondrial functions that lead to energy deprivation, redox imbalance, and cell dysfunction. (10, by permission.)
Figure 2. Figure 2. Endogenous sources of ROS signal. Intracellular ROS is primarily produced by NADPH oxidase enzymes (NOXs), the mitochondria, the endoplasmic reticulum, and the peroxisome. Cytosolic superoxide is rapidly converted into hydrogen peroxide (H2O2) by superoxide dismutase 1 (SOD1). H2O2 can either act as a signaling molecule by oxidizing critical thiols within proteins to regulate biological processes, including metabolic adaptation, differentiation, and proliferation or be detoxified to water (H2O) by the scavenging enzymes peroxiredoxin (PRX), GPx, and CAT. In addition, H2O2 can react with metal cations (Fe+2 or Cu+) to generate the hydroxyl radical (OH·), which causes oxidative damage to lipids, proteins, and DNA. (155, by permission).
Figure 3. Figure 3. Hypoxia activates HIF‐1. HIF1α subunit is hydroxylated by prolyl hydroxylase at distinct proline residues thereby targeting the protein for von Hippel‐Lindau protein (pVHL)‐mediated proteasomal degradation. Hypoxia concomitantly diminishes PHD2 activity and induces the production of mitochondrial ROS at complex III resulting in an inhibition of hydroxylation of HIF1α subunit. Once HIF1α subunit is stabilized, it binds with HIF‐β and p300 coactivators to HREs in the promoters and enhancers of target genes that modulate metabolism. (203, by permission).
Figure 4. Figure 4. Summary of hyperoxia signaling pathways in cells. Summary of hyperoxia signaling pathways in cells. activator protein‐1 (AP‐1); growth arrest and DNA damage (GADD); HO‐1; intracellular adhesion molecule (ICAM); insulin‐like growth factor (IGF); interleukin (IL); keratinocyte growth factor (KdcsGF); MAPK; nuclear factor κB (NFκB); poly (ADP‐ribosyl) polymerase (PARP); protein kinase C (PKC); reactive oxygen species (ROS); superoxide oxide dismutase (SOD); tumor necrosis factor α(TNF‐α); vascular endothelial cell growth factor (VEGF). (105, by permission.)
Figure 5. Figure 5. Overview on therapeutic mechanisms of HBO2 related to elevations of tissue oxygen tensions. The figure outlines initial effects (denoted by boxes) that occur due to increased production of ROS and RNS and their consequences. Other abbreviations: growth factor (GH), VEGF, HIF, stem/progenitor cells (SPCs), HO‐1, heat‐shock proteins (HSP). (184, by permission.)
Figure 6. Figure 6. HIF target genes. The HIF transcription factor regulates the expression of a number of genes involved in many cellular functions, including inflammation, proliferation, survival, metabolism and mitochondrial function, extracellular matrix function, motility, and angiogenesis. carbonic anhydrase IX (CAIX); C‐X‐C chemokine receptor 4 (CXCR4); insulin‐like growth factor II (IGF‐2); metastasis (MET); PDGF B; pyruvate dehydrogenase kinase 1 (PDK1); stromal cell‐derived factor 1alpha (SDF1alpha); vascular endothelial growth factor A (VEGFA). (13, by permission.)
Figure 7. Figure 7. Ketone ester delays hyperoxia‐induced seizures. Example of EEG raw data acquisition after the administration of water (n = 38) (A), butanediol BD (n = 6) (B), and ketone ester BD‐AcAc2 (n = 16) (C). Test substances were administered 30 min before 5 ATA O2. (D) Percent change in latency to seizure (LS) (means SE) relative to control. Oral administration of BD‐AcAc2 caused a significant increase in LS at 5 ATA O2 compared with water or BD (P 0.001). (E) Individual responses in LS of rats in control, BD, and DB‐AcAc2 groups. ***Significance (P 0.001) of BD‐AcAc2 group from control (water) treated and BD‐treated animals as determined by t test. (37, by permission.)
Figure 8. Figure 8. Suppression of tumor growth with HBO and KD therapy. (A) Representative animals from each treatment group demonstrating tumor bioluminescence at day 21 after tumor cell inoculation. Treated animals showed less bioluminescence than controls with KD+HBOT mice exhibiting a profound decrease in tumor bioluminescence compared to all groups. (B) Total body bioluminescence was measured weekly as a measure of tumor size; error bars represent ±SEM. KD+HBOT mice exhibited significantly less tumor bioluminescence than control animals at week 3 (P = 0.0062; two‐tailed student's t test) and an overall trend of notably slower tumor growth than controls and other treated animals throughout the study. (C, D) Day 21 ex vivo organ bioluminescence of SD and KD+HBOT animals (N = 8) demonstrated a trend of reduced metastatic tumor burden in animals receiving the combined therapy. Spleen bioluminescence was significantly decreased in KD+HBOT mice (*P = 0.0266; two‐tailed student's t test). Results were considered significant when P < 0.05. (151, by permission.)


Figure 1. Mitochondrial RONS production—OxS versus signaling. The mitochondrion is implicated in the generation of ROS and RNS. In most cells, the mitochondrial respiratory chain is recognized as the major site of RONS production in the form of superoxide, hydrogen peroxide and the hydroxyl radical. These RONS are considered important for normal cell signaling. However, excessive amounts of RONS are deleterious for the cell, contributing to a variety of pathological processes. RONS production can result in the setup of a vicious cycle of oxidative damage causing a progressive alteration of mtDNA and mitochondrial functions that lead to energy deprivation, redox imbalance, and cell dysfunction. (10, by permission.)


Figure 2. Endogenous sources of ROS signal. Intracellular ROS is primarily produced by NADPH oxidase enzymes (NOXs), the mitochondria, the endoplasmic reticulum, and the peroxisome. Cytosolic superoxide is rapidly converted into hydrogen peroxide (H2O2) by superoxide dismutase 1 (SOD1). H2O2 can either act as a signaling molecule by oxidizing critical thiols within proteins to regulate biological processes, including metabolic adaptation, differentiation, and proliferation or be detoxified to water (H2O) by the scavenging enzymes peroxiredoxin (PRX), GPx, and CAT. In addition, H2O2 can react with metal cations (Fe+2 or Cu+) to generate the hydroxyl radical (OH·), which causes oxidative damage to lipids, proteins, and DNA. (155, by permission).


Figure 3. Hypoxia activates HIF‐1. HIF1α subunit is hydroxylated by prolyl hydroxylase at distinct proline residues thereby targeting the protein for von Hippel‐Lindau protein (pVHL)‐mediated proteasomal degradation. Hypoxia concomitantly diminishes PHD2 activity and induces the production of mitochondrial ROS at complex III resulting in an inhibition of hydroxylation of HIF1α subunit. Once HIF1α subunit is stabilized, it binds with HIF‐β and p300 coactivators to HREs in the promoters and enhancers of target genes that modulate metabolism. (203, by permission).


Figure 4. Summary of hyperoxia signaling pathways in cells. Summary of hyperoxia signaling pathways in cells. activator protein‐1 (AP‐1); growth arrest and DNA damage (GADD); HO‐1; intracellular adhesion molecule (ICAM); insulin‐like growth factor (IGF); interleukin (IL); keratinocyte growth factor (KdcsGF); MAPK; nuclear factor κB (NFκB); poly (ADP‐ribosyl) polymerase (PARP); protein kinase C (PKC); reactive oxygen species (ROS); superoxide oxide dismutase (SOD); tumor necrosis factor α(TNF‐α); vascular endothelial cell growth factor (VEGF). (105, by permission.)


Figure 5. Overview on therapeutic mechanisms of HBO2 related to elevations of tissue oxygen tensions. The figure outlines initial effects (denoted by boxes) that occur due to increased production of ROS and RNS and their consequences. Other abbreviations: growth factor (GH), VEGF, HIF, stem/progenitor cells (SPCs), HO‐1, heat‐shock proteins (HSP). (184, by permission.)


Figure 6. HIF target genes. The HIF transcription factor regulates the expression of a number of genes involved in many cellular functions, including inflammation, proliferation, survival, metabolism and mitochondrial function, extracellular matrix function, motility, and angiogenesis. carbonic anhydrase IX (CAIX); C‐X‐C chemokine receptor 4 (CXCR4); insulin‐like growth factor II (IGF‐2); metastasis (MET); PDGF B; pyruvate dehydrogenase kinase 1 (PDK1); stromal cell‐derived factor 1alpha (SDF1alpha); vascular endothelial growth factor A (VEGFA). (13, by permission.)


Figure 7. Ketone ester delays hyperoxia‐induced seizures. Example of EEG raw data acquisition after the administration of water (n = 38) (A), butanediol BD (n = 6) (B), and ketone ester BD‐AcAc2 (n = 16) (C). Test substances were administered 30 min before 5 ATA O2. (D) Percent change in latency to seizure (LS) (means SE) relative to control. Oral administration of BD‐AcAc2 caused a significant increase in LS at 5 ATA O2 compared with water or BD (P 0.001). (E) Individual responses in LS of rats in control, BD, and DB‐AcAc2 groups. ***Significance (P 0.001) of BD‐AcAc2 group from control (water) treated and BD‐treated animals as determined by t test. (37, by permission.)


Figure 8. Suppression of tumor growth with HBO and KD therapy. (A) Representative animals from each treatment group demonstrating tumor bioluminescence at day 21 after tumor cell inoculation. Treated animals showed less bioluminescence than controls with KD+HBOT mice exhibiting a profound decrease in tumor bioluminescence compared to all groups. (B) Total body bioluminescence was measured weekly as a measure of tumor size; error bars represent ±SEM. KD+HBOT mice exhibited significantly less tumor bioluminescence than control animals at week 3 (P = 0.0062; two‐tailed student's t test) and an overall trend of notably slower tumor growth than controls and other treated animals throughout the study. (C, D) Day 21 ex vivo organ bioluminescence of SD and KD+HBOT animals (N = 8) demonstrated a trend of reduced metastatic tumor burden in animals receiving the combined therapy. Spleen bioluminescence was significantly decreased in KD+HBOT mice (*P = 0.0266; two‐tailed student's t test). Results were considered significant when P < 0.05. (151, by permission.)
References
 1.Abe M, Shioyama Y, Terashima K, Matsuo M, Hara I, Uehara S. Successful hyperbaric oxygen therapy for laryngeal radionecrosis after chemoradiotherapy for mesopharyngeal cancer: Case report and literature review. Jpn J Radiol 30: 340‐344, 2012.
 2.Al‐Waili NS, Butler GJ, Beale J, Hamilton RW, Lee BY, Lucas P. Hyperbaric oxygen and malignancies: A potential role in radiotherapy, chemotherapy, tumor surgery and phototherapy. Med Sci Monit 11: RA279‐RA289, 2005.
 3.Allen BW, Demchenko IT, Piantadosi CA. Two faces of nitric oxide: Implications for cellular mechanisms of oxygen toxicity. J Appl Physiol (1985) 106: 662‐667, 2009.
 4.Alleva R, Nasole E, Di Donato F, Borghi B, Neuzil J, Tomasetti M. alpha‐Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy. Biochem Biophys Res Commun 333: 404‐410, 2005.
 5.Almzaiel AJ, Billington R, Smerdon G, Moody AJ. Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL‐60 (neutrophil‐like) cells. Life Sci 93: 125‐131, 2013.
 6.Arieli Y, Kotler D, Eynan M, Hochman A. Hyperbaric oxygen preconditioning protects rats against CNS oxygen toxicity. Respir Physiol Neurobiol 197: 29‐35, 2014.
 7.Asano T, Kaneko E, Shinozaki S, Imai Y, Shibayama M, Chiba T, Ai M, Kawakami A, Asaoka H, Nakayama T, Mano Y, Shimokado K. Hyperbaric oxygen induces basic fibroblast growth factor and hepatocyte growth factor expression, and enhances blood perfusion and muscle regeneration in mouse ischemic hind limbs. Circ J 71: 405‐411, 2007.
 8.Baynosa RC, Naig AL, Murphy PS, Fang XH, Stephenson LL, Khiabani KT, Wang WZ, Zamboni WA. The effect of hyperbaric oxygen on nitric oxide synthase activity and expression in ischemia‐reperfusion injury. J Surg Res 183: 355‐361, 2013.
 9.Baynosa RC, Zamboni WA. The effect of hyperbaric oxygen on compromised grafts and flaps. Undersea Hyperb Med 39: 857‐865, 2012.
 10.Bellance N, Lestienne P, Rossignol R. Mitochondria: From bioenergetics to the metabolic regulation of carcinogenesis. Front Biosci (Landmark Ed) 14: 4015‐4034, 2009.
 11.Benson RM, Minter LM, Osborne BA, Granowitz EV. Hyperbaric oxygen inhibits stimulus‐induced proinflammatory cytokine synthesis by human blood‐derived monocyte‐macrophages. Clin Exp Immunol 134: 57‐62, 2003.
 12.Bert P HM, Hitchcock FA. Barometric Pressure. Columbus, Ohio: College Book Company, 1943.
 13.Bertout JA, Patel SA, Simon MC. The impact of O2 availability on human cancer. Nat Rev Cancer 8: 967‐975, 2008.
 14.Bhutani S, Vishwanath G. Hyperbaric oxygen and wound healing. Indian J Plast Surg 45: 316‐324, 2012.
 15.Bitterman H. Bench‐to‐bedside review: Oxygen as a drug. Crit Care 13: 205, 2009.
 16.Bitterman N, Skapa E, Gutterman A. Starvation and dehydration attenuate CNS oxygen toxicity in rats. Brain Res 761: 146‐150, 1997.
 17.Boadi WY, Thaire L, Kerem D, Yannai S. Effects of dietary supplementation with vitamin E, riboflavin and selenium on central nervous system oxygen toxicity. Pharmacol Toxicol 68: 77‐82, 1991.
 18.Brown GC, Borutaite V. There is no evidence that mitochondria are the main source of reactive oxygen species in mammalian cells. Mitochondrion 12: 1‐4, 2012.
 19.Butler FK, Jr. Closed‐circuit oxygen diving in the U.S. Navy. Undersea Hyperb Med 31: 3‐20, 2004.
 20.Butler FK, Jr, Knafelc ME. Screening for oxygen intolerance in U.S. Navy divers. Undersea Biomed Res 13: 91‐98, 1986.
 21.Caldwell PR, Lee WL, Jr., Schildkraut HS, Archibald ER. Changes in lung volume, diffusing capacity, and blood gases in men breathing oxygen. J Appl Physiol 21: 1477‐1483, 1966.
 22.Cameron L, Pilcher J, Weatherall M, Beasley R, Perrin K. The risk of serious adverse outcomes associated with hypoxaemia and hyperoxaemia in acute exacerbations of COPD. Postgrad Med J 88: 684‐689, 2012.
 23.Camporesi EM, Bosco G. Hyperbaric oxygen pretreatment and preconditioning. Undersea Hyperb Med 41: 259‐263, 2014.
 24.Cassandra EF, Stephen DP, Maria Luz F, Erin EQ, Richard JW, Doug MB, William JK, Richard DF, Jeff SV. Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation. Lipids 43: 65‐77, 2007.
 25.Chavko M, Harabin AL. Regional lipid peroxidation and protein oxidation in rat brain after hyperbaric oxygen exposure. Free Radic Biol Med 20: 973‐978, 1996.
 26.Chen LF, Tian YF, Lin CH, Huang LY, Niu KC, Lin MT. Repetitive hyperbaric oxygen therapy provides better effects on brain inflammation and oxidative damage in rats with focal cerebral ischemia. J Formos Med Assoc 113: 620‐628, 2014.
 27.Chen SJ, Yu CT, Cheng YL, Yu SY, Lo HC. Effects of hyperbaric oxygen therapy on circulating interleukin‐8, nitric oxide, and insulin‐like growth factors in patients with type 2 diabetes mellitus. Clin Biochem 40: 30‐36, 2007.
 28.Chen X, Duan XS, Xu LJ, Zhao JJ, She ZF, Chen WW, Zheng ZJ, Jiang GD. Interleukin‐10 mediates the neuroprotection of hyperbaric oxygen therapy against traumatic brain injury in mice. Neuroscience 266: 235‐243, 2014.
 29.Cheng O, Ostrowski RP, Wu B, Liu W, Chen C, Zhang JH. Cyclooxygenase‐2 mediates hyperbaric oxygen preconditioning in the rat model of transient global cerebral ischemia. Stroke 42: 484‐490, 2011.
 30.Ciencewicki J, Trivedi S, Kleeberger SR. Oxidants and the pathogenesis of lung diseases. J Allergy Clin Immunol 122: 456‐468; quiz 469‐470, 2008.
 31.Claireaux AE. The effect of oxygen on the lung. J Clin Pathol Suppl (R Coll Pathol) 9: 75‐80, 1975.
 32.Clark JM, Lambertsen CJ. Pulmonary oxygen toxicity: A review. Pharmacol Rev 23: 37‐133, 1971.
 33.Comroe JHJ, Dumke PR, Deming M. Oxygen toxicity: The effects of inhalation of high concentrations of oxygen for twenty‐four hours on normal men at sea level and at a simulated altitude of 18,000 feet. JAMA 128(10): 710‐717, 1945.
 34.Crapo JD. Morphologic changes in pulmonary oxygen toxicity. Annu Rev Physiol 48: 721‐731, 1986.
 35.Crapo JD, Barry BE, Foscue HA, Shelburne J. Structural and biochemical changes in rat lungs occurring during exposures to lethal and adaptive doses of oxygen. Am Rev Respir Dis 122: 123‐143, 1980.
 36.D'Agostino D, Olson J, Dean J. Acute hyperoxia increases lipid peroxidation and induces plasma membrane blebbing in human U87 glioblastoma cells. Neuroscience 159: 1011‐1033, 2009.
 37.D'Agostino DP, Pilla R, Held HE, Landon CS, Puchowicz M, Brunengraber H, Ari C, Arnold P, Dean JB. Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats. Am J Physiol Regul Integr Comp Physiol 304: R829‐R836, 2013.
 38.D'Autreaux B, Toledano MB. ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8: 813‐824, 2007.
 39.Daruwalla J, Christophi C. Hyperbaric oxygen therapy for malignancy: A review. World J Surg 30: 2112‐2143, 2006.
 40.Davies KJ, Goldberg AL. Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes. J Biol Chem 262: 8220‐8226, 1987.
 41.Davis LM, Pauly JR, Readnower RD, Rho JM, Sullivan PG. Fasting is neuroprotective following traumatic brain injury. J Neurosci Res 86: 1812‐1822, 2008.
 42.Dean JB. Hypercapnia causes cellular oxidation and nitrosation in addition to acidosis: Implications for CO2 chemoreceptor function and dysfunction. J Appl Physiol (1985) 108: 1786‐1795, 2010.
 43.Dean JB, Mulkey DK, Garcia AJ, III, Putnam RW, Henderson RA, III. Neuronal sensitivity to hyperoxia, hypercapnia, and inert gases at hyperbaric pressures. J Appl Physiol (1985) 95: 883‐909, 2003.
 44.Dean JB, Mulkey DK, Henderson RA, III, Potter SJ, Putnam RW. Hyperoxia, reactive oxygen species, and hyperventilation: Oxygen sensitivity of brain stem neurons. J Appl Physiol (1985) 96: 784‐791, 2004.
 45.Demchenko IT, Luchakov YI, Moskvin AN, Gutsaeva DR, Allen BW, Thalmann ED, Piantadosi CA. Cerebral blood flow and brain oxygenation in rats breathing oxygen under pressure. J Cereb Blood Flow Metab 25: 1288‐1300, 2005.
 46.Demchenko IT, Welty‐Wolf KE, Allen BW, Piantadosi CA. Similar but not the same: Normobaric and hyperbaric pulmonary oxygen toxicity, the role of nitric oxide. Am J Physiol Lung Cell Mol Physiol 293: L229‐L238, 2007.
 47.Demchenko IT, Zhilyaev SY, Moskvin AN, Krivchenko AI, Piantadosi CA, Allen BW. Baroreflex‐mediated cardiovascular responses to hyperbaric oxygen. J Appl Physiol (1985) 115: 819‐828, 2013.
 48.Demple B, Harrison L. Repair of oxidative damage to DNA: Enzymology and biology. Annu Rev Biochem 63: 915‐948, 1994.
 49.Dennog C, Hartmann A, Frey G, Speit G. Detection of DNA damage after hyperbaric oxygen (HBO) therapy. Mutagenesis 11: 605‐609, 1996.
 50.Dennog C, Radermacher P, Barnett YA, Speit G. Antioxidant status in humans after exposure to hyperbaric oxygen. Mutat Res 428: 83‐89, 1999.
 51.Dirks RC, Faiman MD. Free radical formation and lipid peroxidation in rat and mouse cerebral cortex slices exposed to high oxygen pressure. Brain Res 248: 355‐360, 1982.
 52.Donald KW. Oxygen poisoning in man. Br Med J 1: 667, 1947.
 53.Elayan IM, Axley MJ, Prasad PV, Ahlers ST, Auker CR. Effect of hyperbaric oxygen treatment on nitric oxide and oxygen free radicals in rat brain. J Neurophysiol 83: 2022‐2029, 2000.
 54.Erecinska M, Silver IA. Tissue oxygen tension and brain sensitivity to hypoxia. Respir Physiol 128: 263‐276, 2001.
 55.Feldmeier J CU, Hartmann K. Hyperbaric oxygen: does it promote growth or recurrence of malignancy?, 30: 1‐18, 2003.
 56.Fenech M, Holland N, Chang WP, Zeiger E, Bonassi S. The HUman MicroNucleus Project–An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res 428: 271‐283, 1999.
 57.Fildissis G, Venetsanou K, Myrianthefs P, Karatzas S, Zidianakis V, Baltopoulos G. Whole blood pro‐inflammatory cytokines and adhesion molecules post‐lipopolysaccharides exposure in hyperbaric conditions. Eur Cytokine Netw 15: 217‐221, 2004.
 58.Freeman BA, Crapo JD. Biology of disease: Free radicals and tissue injury. Lab Invest 47: 412‐426, 1982.
 59.Gabb G, Robin ED. Hyperbaric oxygen. A therapy in search of diseases. Chest 92: 1074‐1082, 1987.
 60.Gallagher KA, Liu ZJ, Xiao M, Chen H, Goldstein LJ, Buerk DG, Nedeau A, Thom SR, Velazquez OC. Diabetic impairments in NO‐mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF‐1 alpha. J Clin Invest 117: 1249‐1259, 2007.
 61.Garcia AJ, III, Putnam RW, Dean JB. Hyperbaric hyperoxia and normobaric reoxygenation increase excitability and activate oxygen‐induced potentiation in CA1 hippocampal neurons. J Appl Physiol (1985) 109: 804‐819, 2010.
 62.Gerschman R, Gilbert DL, Nye SW, Dwyer P, Fenn WO. Oxygen poisoning and x‐irradiation: A mechanism in common. Science 119: 623‐626, 1954.
 63.Gill AL, Bell CNA. Hyperbaric oxygen: Its uses, mechanisms of action and outcomes. QJM 97, 385‐395, 2004.
 64.Godman CA, Joshi R, Giardina C, Perdrizet G, Hightower LE. Hyperbaric oxygen treatment induces antioxidant gene expression. Ann N Y Acad Sci 1197: 178‐183, 2010.
 65.Groesbeck DK, Bluml RM, Kossoff EH. Long‐term use of the ketogenic diet in the treatment of epilepsy. Dev Med Child Neurol 48: 978‐981, 2006.
 66.Gu G‐JJ, Li Y‐PP, Peng Z‐YY, Xu J‐JJ, Kang Z‐MM, Xu W‐GG, Tao H‐YY, Ostrowski RP, Zhang JH, Sun X‐JJ. Mechanism of ischemic tolerance induced by hyperbaric oxygen preconditioning involves upregulation of hypoxia‐inducible factor‐1alpha and erythropoietin in rats. J Appl Physiol (Bethesda, Md: 1985) 104: 1185‐1191, 2008.
 67.Gurdol F, Cimsit M, Oner‐Iyidogan Y, Kocak H, Sengun S, Yalcinkaya‐Demirsoz S. Collagen synthesis, nitric oxide and asymmetric dimethylarginine in diabetic subjects undergoing hyperbaric oxygen therapy. Physiol Res 59: 423‐429, 2010.
 68.Halperin EC, Brady LW, Perez CA, Wazer DE. Principles and Practice of Radiation Oncology. Philadelphia: Lippincott Williams and Wilkins, 2008.
 69.Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med 368: 1162‐1163, 2013.
 70.Heyboer M, III, Milovanova TN, Wojcik S, Grant W, Chin M, Hardy KR, Lambert DS, Logue C, Thom SR. CD34+/CD45‐dim stem cell mobilization by hyperbaric oxygen—changes with oxygen dosage. Stem Cell Res 12: 638‐645, 2014.
 71.Hileman EO, Liu J, Albitar M, Keating MJ, Huang P. Intrinsic oxidative stress in cancer cells: A biochemical basis for therapeutic selectivity. Cancer Chemother Pharmacol 53: 209‐219, 2004.
 72.Hite AH, Berkowitz VG, Berkowitz K. Low‐carbohydrate diet review: Shifting the paradigm. Nutr Clin Pract 26: 300‐308, 2011.
 73.Hodgson JC, Watkins CA, Bayne CW. Contribution of respiratory burst activity to innate immune function and the effects of disease status and agent on chemiluminescence responses by ruminant phagocytes in vitro. Vet Immunol Immunopathol 112: 12‐23, 2006.
 74.Holmstrom KM, Finkel T. Cellular mechanisms and physiological consequences of redox‐dependent signalling. Nat Rev Mol Cell Biol 15: 411‐421, 2014.
 75.Hu Q, Liang X, Chen D, Chen Y, Doycheva D, Tang J, Tang J, Zhang JH. Delayed hyperbaric oxygen therapy promotes neurogenesis through reactive oxygen species/hypoxia‐inducible factor‐1α/β‐catenin pathway in middle cerebral artery occlusion rats. Stroke 45: 1807‐1814, 2014.
 76.Hu S, Li F, Luo H, Xia Y, Zhang J, Hu R, Cui G, Meng H, Feng H. Amelioration of rCBF and PbtO2 following TBI at high altitude by hyperbaric oxygen pre‐conditioning. Neurol Res 32: 173‐178, 2010.
 77.Hu SL, Hu R, Li F, Liu Z, Xia YZ, Cui GY, Feng H. Hyperbaric oxygen preconditioning protects against traumatic brain injury at high altitude. Acta Neurochir Suppl 105: 191‐196, 2007.
 78.Hunt TK, Aslam RS, Beckert S, Wagner S, Ghani QP, Hussain MZ, Roy S, Sen CK. Aerobically derived lactate stimulates revascularization and tissue repair via redox mechanisms. Antioxid Redox Signal 9: 1115‐1124, 2007.
 79.Jadhav V, Ostrowski RP, Tong W, Matus B, Chang C, Zhang JH. Hyperbaric oxygen preconditioning reduces postoperative brain edema and improves neurological outcomes after surgical brain injury. Acta Neurochir Suppl 106: 217‐220, 2010.
 80.Jadhav V, Solaroglu I, Obenaus A, Zhang JH. Neuroprotection against surgically induced brain injury. Surg Neurol 67: 15‐20; discussion 20, 2007.
 81.Jamieson D. Oxygen toxicity and reactive oxygen metabolites in mammals. Free Radic Biol Med 7: 87‐108, 1989.
 82.Jarrett SG, Milder JB, Liang LP, Patel M. The ketogenic diet increases mitochondrial glutathione levels. J Neurochem 106: 1044‐1051, 2008.
 83.Jerrett SA, Jefferson D, Mengel CE. Seizures, H2O2 formation and lipid peroxides in brain during exposure to oxygen under high pressure. Aerosp Med 44: 40‐44, 1973.
 84.Jyonouchi H, Sun S, Abiru T, Chareancholvanich S, Ingbar DH. The effects of hyperoxic injury and antioxidant vitamins on death and proliferation of human small airway epithelial cells. Am J Respir Cell Mol Biol 19: 426‐436, 1998.
 85.Kamata H, Honda S, Maeda S, Chang LF, Hirata H, Karin M. Reactive oxygen species promote TNF alpha‐induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120: 649‐661, 2005.
 86.Kang TS, Gorti GK, Quan SY, Ho M, Koch RJ. Effect of hyperbaric oxygen on the growth factor profile of fibroblasts. Arch Facial Plast Surg 6: 31‐35, 2004.
 87.Kashiwaya Y, Bergman C, Lee JH, Wan R, King MT, Mughal MR, Okun E, Clarke K, Mattson MP, Veech RL. A ketone ester diet exhibits anxiolytic and cognition‐sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease. Neurobiol Aging 34: 1530‐1539, 2013.
 88.Kashiwaya Y, Sato K, Tsuchiya N, Thomas S, Fell DA, Veech RL, Passonneau JV. Control of glucose utilization in working perfused rat heart. J Biol Chem 269: 25502‐25514, 1994.
 89.Kazzaz JA, Xu J, Palaia TA, Mantell L, Fein AM, Horowitz S. Cellular oxygen toxicity. Oxidant injury without apoptosis. J Biol Chem 271: 15182‐15186, 1996.
 90.Kerr JS, Chae CU, Nagase H, Berg RA, Riley DJ. Degradation of collagen in lung tissue slices exposed to hyperoxia. Am Rev Respir Dis 135: 1334‐1339, 1987.
 91.Kesl S, Jung M, Prather J, Sherwood J, Gould L, D'Agostino D. Sustaining dietary ketosis to improve blood flow and wound healing in young and aged Fisher rats. FASEB J 28(1 Supplement): 734.7, 2014.
 92.Kim do Y, Davis LM, Sullivan PG, Maalouf M, Simeone TA, van Brederode J, Rho JM. Ketone bodies are protective against oxidative stress in neocortical neurons. J Neurochem 101: 1316‐1326, 2007.
 93.Kim HR, Kim JH, Choi EJ, Lee YK, Kie JH, Jang MH, Seoh JY. Hyperoxygenation attenuated a murine model of atopic dermatitis through raising skin level of ROS. PLoS One 9: e109297, 2014.
 94.Kirino T, Tsujita Y, Tamura A. Induced tolerance to ischemia in gerbil hippocampal neurons. J Cereb Blood Flow Metab 11: 299‐307, 1991.
 95.Kistler GS, Caldwell PR, Weibel ER. Development of fine structural damage to alveolar and capillary lining cells in oxygen‐poisoned rat lungs. J Cell Biol 32: 605‐628, 1967.
 96.Korhonen K. Hyperbaric oxygen therapy in acute necrotizing infections. With a special reference to the effects on tissue gas tensions. Ann Chir Gynaecol 89(Suppl 214): 7‐36, 2000.
 97.Kovachich GB, Mishra OP. Lipid peroxidation in rat brain cortical slices as measured by the thiobarbituric acid test. J Neurochem 35: 1449‐1452, 1980.
 98.Kutlay M, Colak A, Yildiz S, Demircan N, Akin ON. Stereotactic aspiration and antibiotic treatment combined with hyperbaric oxygen therapy in the management of bacterial brain abscesses. Neurosurgery 62(Suppl 2): 540‐546, 2008.
 99.Labrouche S, Javorschi S, Leroy D, Gbikpi‐Benissan G, Freyburger G. Influence of hyperbaric oxygen on leukocyte functions and haemostasis in normal volunteer divers. Thromb Res 96: 309‐315, 1999.
 100.Lahat N, Bitterman H, Yaniv N, Kinarty A, Bitterman N. Exposure to hyperbaric oxygen induces tumour necrosis factor‐alpha (TNF‐alpha) secretion from rat macrophages. Clin Exp Immunol 102: 655‐659, 1995.
 101.Lambertsen CJ. Effects of oxygen at high partial pressure. In: Handbook of Physiology, Section 3: Respiration. New York: Marcel Dekker, 1978, pp. 232‐303.
 102.Leach RM, Rees PJ, Wilmshurst P. Hyperbaric oxygen therapy. BMJ 317: 1140‐1143, 1998.
 103.Lee PJ, Alam J, Wiegand GW, Choi AM. Overexpression of heme oxygenase‐1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia. Proc Natl Acad Sci U S A 93: 10393‐10398, 1996.
 104.Lee PJ, Camhi SL, Chin BY, Alam J, Choi AM. AP‐1 and STAT mediate hyperoxia‐induced gene transcription of heme oxygenase‐1. Am J Physiol Lung Cell Mol Physiol 279: L175‐L182, 2000.
 105.Lee PJ, Choi AM. Pathways of cell signaling in hyperoxia. Free Radic Biol Med 35: 341‐350, 2003.
 106.Lee SR, Yang KS, Kwon J, Lee C, Jeong W, Rhee SG. Reversible inactivation of the tumor suppressor PTEN by H2O2. J Biol Chem 277: 20336‐20342, 2002.
 107.Li HF, Zou Y, Ding G. Therapeutic success of the ketogenic diet as a treatment option for epilepsy: A meta‐analysis. Iran J Pediatr 23: 613‐620, 2013.
 108.Li Y, Zhou C, Calvert JW, Colohan AR, Zhang JH. Multiple effects of hyperbaric oxygen on the expression of HIF‐1 alpha and apoptotic genes in a global ischemia‐hypotension rat model. Exp Neurol 191: 198‐210, 2005.
 109.Lin K‐CC, Niu K‐CC, Tsai K‐JJ, Kuo J‐RR, Wang L‐CC, Chio C‐CC, Chang C‐PP. Attenuating inflammation but stimulating both angiogenesis and neurogenesis using hyperbaric oxygen in rats with traumatic brain injury. J Trauma Acute Care Surg 72: 650‐659, 2012.
 110.Lin S, Shyu KG, Lee CC, Wang BW, Chang CC, Liu YC, Huang FY, Chang H. Hyperbaric oxygen selectively induces angiopoietin‐2 in human umbilical vein endothelial cells. Biochem Biophys Res Commun 296: 710‐715, 2002.
 111.Liu W, Zhang J, Ma C, Liu Y, Li R, Sun X, Zhang J, Xu WG. Dual effects of hyperbaric oxygen on proliferation and cytotoxic T lymphocyte activity of rat splenic lymphocytes. Undersea Hyperb Med 36: 155‐160, 2009.
 112.Loboda A, Jozkowicz A, Dulak J. HIF‐1 and HIF‐2 transcription factors—similar but not identical. Mol Cells 29: 435‐442, 2010.
 113.Lodhi IJ, Semenkovich CF. Peroxisomes: A nexus for lipid metabolism and cellular signaling. Cell Metabolism 19: 380‐392, 2014.
 114.Lum J, Bui T, Gruber M, Gordan J, DeBerardinis R, Covello K, Simon M, Thompson C. The transcription factor HIF‐1alpha plays a critical role in the growth factor‐dependent regulation of both aerobic and anaerobic glycolysis. Genes Dev 21: 1037‐1049, 2007.
 115.Luongo C, Imperatore F, Cuzzocrea S, Filippelli A, Scafuro MA, Mangoni G, Portolano F, Rossi F. Effects of hyperbaric oxygen exposure on a zymosan‐induced shock model. Crit Care Med 26: 1972‐1976, 1998.
 116.Maalouf M, Rho J, Mattson M. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev 59: 293‐315, 2009.
 117.Maalouf M, Sullivan PG, Davis L, Kim DY, Rho JM. Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience 145: 256‐264, 2007.
 118.Mach WJ, Thimmesch AR, Pierce JT, Pierce JD. Consequences of hyperoxia and the toxicity of oxygen in the lung. Nurs Res Pract 2011: 260482.
 119.Maltepe E, Saugstad OD. Oxygen in health and disease: Regulation of oxygen homeostasis–clinical implications. Pediatr Res 65: 261‐268, 2009.
 120.Marin‐Hernandez A, Gallardo‐Perez JC, Ralph SJ, Rodriguez‐Enriquez S, Moreno‐Sanchez R. HIF‐1alpha modulates energy metabolism in cancer cells by inducing over‐expression of specific glycolytic isoforms. Mini Rev Med Chem 9: 1084‐1101, 2009.
 121.Massey PR, Sakran JV, Mills AM, Sarani B, Aufhauser DD, Jr., Sims CA, Pascual JL, Kelz RR, Holena DN. Hyperbaric oxygen therapy in necrotizing soft tissue infections. J Surg Res 177: 146‐151, 2012.
 122.Matott MP, Ciarlone GE, Putnam RW, Dean JB. Normobaric hyperoxia (95% O(2)) stimulates CO(2)‐sensitive and CO(2)‐insensitive neurons in the caudal solitary complex of rat medullary tissue slices maintained in 40% O(2). Neuroscience 270: 98‐122, 2014.
 123.Matsunami T, Sato Y, Sato T, Ariga S, Shimomura T, Yukawa M. Oxidative stress and gene expression of antioxidant enzymes in the streptozotocin‐induced diabetic rats under hyperbaric oxygen exposure. Int J Clin Exp Pathol 3: 177‐188, 2009.
 124.Matsunami T, Sato Y, Sato T, Yukawa M. Antioxidant status and lipid peroxidation in diabetic rats under hyperbaric oxygen exposure. Physiol Res 59: 97‐104, 2010.
 125.Medan D, Wang L, Toledo D, Lu B, Stehlik C, Jiang BH, Shi X, Rojanasakul Y. Regulation of Fas (CD95)‐induced apoptotic and necrotic cell death by reactive oxygen species in macrophages. J Cell Physiol 203: 78‐84, 2005.
 126.Mehta JL, Li DY. Inflammation in ischemic heart disease: Response to tissue injury or a pathogenetic villain? Cardiovasc Res 43: 291‐299, 1999.
 127.Meng TC, Fukada T, Tonks NK. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Molecular Cell 9: 387‐399, 2002.
 128.Milovanova TN, Bhopale VM, Sorokina EM, Moore JS, Hunt TK, Hauer‐Jensen M, Velazquez OC, Thom SR. Lactate stimulates vasculogenic stem cells via the thioredoxin system and engages an autocrine activation loop involving hypoxia‐inducible factor 1. Mol Cell Biol 28: 6248‐6261, 2008.
 129.Moen I, Stuhr LE. Hyperbaric oxygen therapy and cancer—a review. Target Oncol 7: 233‐242, 2012.
 130.Mulkey DK, Henderson RA, III, Putnam RW, Dean JB. Hyperbaric oxygen and chemical oxidants stimulate CO2/H+‐sensitive neurons in rat brain stem slices. J Appl Physiol (1985) 95: 910‐921, 2003.
 131.Muralidharan V, Christophi C. Hyperbaric oxygen therapy and liver transplantation. HPB (Oxford) 9: 174‐182, 2007.
 132.Narkowicz CK, Vial JH, Mccartney PW. Hyperbaric‐oxygen therapy increases free‐radical levels in the blood of humans. Free Radic Res Commun 19: 71‐80, 1993.
 133.Netea MG, Joosten LA. Inflammasome inhibition: Putting out the fire. Cell Metab 21: 513‐514, 2015.
 134.Neuman TS, Thom SR. Physiology and Medicine of Hyperbaric Oxygen Therapy. Saunders, Philadelphia, PA, 2008.
 135.Niki E. Interaction of ascorbate and alpha‐tocopherol. Ann N Y Acad Sci 498: 186‐199, 1987.
 136.Nishiki K, Jamieson D, Oshino N, Chance B. Oxygen toxicity in the perfused rat liver and lung under hyperbaric conditions. Biochem J 160: 343‐355, 1976.
 137.NOaA A. Scientific Diving Standards and Safety Manual, 2011.
 138.Olbryt M, Jarzab M, Jazowiecka‐Rakus J, Simek K, Szala S, Sochanik A. Gene expression profile of B 16(F10) murine melanoma cells exposed to hypoxic conditions in vitro. Gene Expr 13: 191‐203, 2006.
 139.Olshyk VN, Melsitova IV, Yurkova IL. Influence of lipids with hydroxyl‐containing head groups on Fe2+(Cu2+)/H2O2‐mediated transformation of phospholipids in model membranes. Chem Phys Lipids 177: 1‐7, 2014.
 140.Ostrowski RP, Graupner G, Titova E, Zhang J, Chiu J, Dach N, Corleone D, Tang J, Zhang JH. The hyperbaric oxygen preconditioning‐induced brain protection is mediated by a reduction of early apoptosis after transient global cerebral ischemia. Neurobiol Dis 29: 1‐13, 2008.
 141.Ozben T. Oxidative stress and apoptosis: Impact on cancer therapy. J Pharm Sci 96: 2181‐2277, 2007.
 142.Pagano A, Barazzone‐Argiroffo C. Alveolar cell death in hyperoxia‐induced lung injury. Ann N Y Acad Sci 1010: 405‐416, 2003.
 143.Pagano G, Talamanca AA, Castello G, Cordero MD, d'Ischia M, Gadaleta MN, Pallardo FV, Petrovic S, Tiano L, Zatterale A. Oxidative stress and mitochondrial dysfunction across broad‐ranging pathologies: Toward mitochondria‐targeted clinical strategies. Oxid Med Cell Longev 2014: 541230, 2014.
 144.Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: A review of the therapeutic uses of very‐low‐carbohydrate (ketogenic) diets. Eur J Clin Nutr 67: 789‐796, 2013.
 145.Pasupathy S, Homer‐Vanniasinkam S. Surgical implications of ischemic preconditioning. Arch Surg 140: 405‐409; discussion 410, 2005.
 146.Patel D, Agarwal S, Garg P, Lakhani K. Oxygen toxicity. JIACM 4: 234‐237, 2003.
 147.Peng Z, Ren P, Kang Z, Du J, Lian Q, Liu Y, Zhang JH, Sun X. Up‐regulated HIF‐1alpha is involved in the hypoxic tolerance induced by hyperbaric oxygen preconditioning. Brain Res 1212: 71‐78, 2008.
 148.Pereira AL, Ferreira MR, Santos OJ, Sauaia Filho EN, Paiva AE, Santos RH, Santos RA. Effects of oxygen in lungs of rats. Acta Cir Bras 29: 771‐775, 2014.
 149.Pesa. HBO Therapy for Soft Tissue Radionecrosis, 2011.
 150.Pilla R, Landon CS, Dean JB. A potential early physiological marker for CNS oxygen toxicity: Hyperoxic hyperpnea precedes seizure in unanesthetized rats breathing hyperbaric oxygen. J Appl Physiol (1985) 114: 1009‐1020, 2013.
 151.Poff AM, Ari C, Seyfried TN, D'Agostino DP. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer. PloS One 8: e65522, 2013.
 152.Poff AM, Ward N, Seyfried TN, Arnold P, D'Agostino DP. Non‐toxic metabolic management of metastatic cancer in VM mice: Novel combination of ketogenic diet, ketone supplementation, and hyperbaric oxygen therapy. PLoS One 10: e0127407, 2015.
 153.Portakal O, Ozkaya O, Erden Inal M, Bozan B, Kosan M, Sayek I. Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer patients. Clin Biochem 33: 279‐284, 2000.
 154.Prins ML, Hovda DA. The effects of age and ketogenic diet on local cerebral metabolic rates of glucose after controlled cortical impact injury in rats. J Neurotrauma 26: 1083‐1093, 2009.
 155.Reczek CR, Chandel NS. ROS‐dependent signal transduction. Curr Opin Cell Biol 33: 8‐13, 2015.
 156.Romashko J, III, Horowitz S, Franek WR, Palaia T, Miller EJ, Lin A, Birrer MJ, Scott W, Mantell LL. MAPK pathways mediate hyperoxia‐induced oncotic cell death in lung epithelial cells. Free Radic Biol Med 35: 978‐993, 2003.
 157.Rothfuss A, Dennog C, Speit G. Adaptive protection against the induction of oxidative DNA damage after hyperbaric oxygen treatment. Carcinogenesis 19: 1913‐1917, 1998.
 158.Saito K, Tanaka Y, Ota T, Eto S, Yamashita U. Suppressive effect of hyperbaric oxygenation on immune responses of normal and autoimmune mice. Clin Exp Immunol 86: 322‐327, 1991.
 159.Schroedl C, McClintock DS, Budinger GR, Chandel NS. Hypoxic but not anoxic stabilization of HIF‐1alpha requires mitochondrial reactive oxygen species. Lung Cell Mol Physiol 283: 31, 2002.
 160.Semenza GL. HIF‐1 and mechanisms of hypoxia sensing. Curr Opin Cell Biol 13: 167‐171, 2001.
 161.Semenza GL. HIF‐1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 123: 3664‐3671, 2013.
 162.Shaikh N, Ummunisa F. Acute management of vascular air embolism. J Emerg Trauma Shock 2: 180‐185, 2009.
 163.Sharman M, Volek J. Weight loss leads to reductions in inflammatory biomarkers after a very‐low‐carbohydrate diet and a low‐fat diet in overweight men. Clin Sci 107: 365‐369, 2004.
 164.Shaw JJ, Psoinos C, Emhoff TA, Shah SA, Santry HP. Not just full of hot air: Hyperbaric oxygen therapy increases survival in cases of necrotizing soft tissue infections. Surg Infect (Larchmt) 15: 328‐335, 2014.
 165.Sheikh AY, Gibson JJ, Rollins MD, Hopf HW, Hussain Z, Hunt TK. Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg 135: 1293‐1297, 2000.
 166.Shen C, Nettleton D, Jiang M, Kim SK, Powell‐Coffman JA. Roles of the HIF‐1 hypoxia‐inducible factor during hypoxia response in Caenorhabditis elegans. J Biol Chem 280: 20580‐20588, 2005.
 167.Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV, Jr., de Cabo R, Ulrich S, Akassoglou K, Verdin E. Suppression of oxidative stress by beta‐hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339: 211‐214, 2013.
 168.Shinohara M, Shang WH, Kubodera M, Harada S, Mitsushita J, Kato M, Miyazaki H, Sumimoto H, Kamata T. Nox1 redox signaling mediates oncogenic Ras‐induced disruption of stress fibers and focal adhesions by down‐regulating Rho. J Biol Chem 282: 17640‐17648, 2007.
 169.Shyu KG, Hung HF, Wang BW, Chang H. Hyperbaric oxygen induces placental growth factor expression in bone marrow‐derived mesenchymal stem cells. Life Sci 83: 65‐73, 2008.
 170.Smith JL. The pathological effects due to increase of oxygen tension in the air breathed. J Physiol 24: 19‐35, 1899.
 171.Undersea and Hyperbaric Medicine Society (UHMS). Indications for Hyperbaric Oxygen Therapy. https://www.uhms.org/resources/hbo-indications.html.
 172.Soejima Y, Ostrowski RP, Manaenko A, Fujii M, Tang J, Zhang JH. Hyperbaric oxygen preconditioning attenuates hyperglycemia enhanced hemorrhagic transformation after transient MCAO in rats. Med Gas Res 2: 9, 2012.
 173.Song XY, Sun LN, Zheng NN, Zhang HP. Effect of hyperbaric oxygen preconditioning on spleen lymphocytes and cell adhesion molecules after skin transplantation in mice. Zhongguo Shi Yan Xue Ye Xue Za Zhi 18: 1275‐1277, 2010.
 174.Speit G, Dennog C, Eichhorn U, Rothfuss A, Kaina B. Induction of heme oxygenase‐1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. Carcinogenesis 21: 1795‐1799, 2000.
 175.Speit G, Dennog C, Lampl L. Biological significance of DNA damage induced by hyperbaric oxygen. Mutagenesis 13: 85‐87, 1998.
 176.Speit G, Dennog C, Radermacher P, Rothfuss A. Genotoxicity of hyperbaric oxygen. Mutat Res 512: 111‐119, 2002.
 177.Srivastava S, Kashiwaya Y, King M, Baxa U, Tam J, Niu G, Chen X, Clarke K, Veech R. Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet. FASEB J 26: 2351‐2362, 2012.
 178.Stetler RA, Leak RK, Gan Y, Li P, Zhang F, Hu X, Jing Z, Chen J, Zigmond MJ, Gao Y. Preconditioning provides neuroprotection in models of CNS disease: Paradigms and clinical significance. Prog Neurobiol 114: 58‐83, 2014.
 179.Sun L, Marti HH, Veltkamp R. Hyperbaric oxygen reduces tissue hypoxia and hypoxia‐inducible factor‐1 alpha expression in focal cerebral ischemia. Stroke 39: 1000‐1006, 2008.
 180.Sunkari VG, Lind F, Botusan IR, Kashif A, Liu ZJ, Yla‐Herttuala S, Brismar K, Velazquez O, Catrina SB. Hyperbaric oxygen therapy activates hypoxia‐inducible factor 1 (HIF‐1), which contributes to improved wound healing in diabetic mice. Wound Repair Regen 23: 98‐103, 2015.
 181.Thom S. Hyperbaric oxygen therapy. J Intensive Care Med 4: 58‐74, 1989.
 182.Thom S, Milavonava T. Adult stem cell mobilization and ischemic site recruitment – redox stress is good. Int Soc Stem Cell Res; Abstract 453: 62, 2008.
 183.Thom SR. Hyperbaric oxygen: Its mechanisms and efficacy. Plast Reconstr Surg 127(Suppl 1): 131S‐141S, 2011.
 184.Thom SR. Oxidative stress is fundamental to hyperbaric oxygen therapy. J Appl Physiol 106: 988‐995, 2009.
 185.Thom SR, Bhopale VM, Velazquez OC, Goldstein LJ, Thom LH, Buerk DG. Stem cell mobilization by hyperbaric oxygen. Am J Physiol Heart Circ Physiol 290: H1378‐H1386, 2006.
 186.Thom SR, Milovanova TN, Yang M, Bhopale VM, Sorokina EM, Uzun G, Malay DS, Troiano MA, Hardy KR, Lambert DS, Logue CJ, Margolis DJ. Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: Increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. Wound Repair Regen 19: 149‐161, 2011.
 187.Thomson L, Paton J. Oxygen toxicity. Paediatr Respir Rev 15: 120‐123, 2014.
 188.Tibbles PM, Edelsberg JS. Hyperbaric‐oxygen therapy. N Engl J Med 334: 1642‐1648, 1996.
 189.Torres‐Gonzalez M, Volek JS, Leite JO, Fraser H, Luz Fernandez M. Carbohydrate restriction reduces lipids and inflammation and prevents atherosclerosis in Guinea pigs. J Atheroscler Thromb 15: 235‐243, 2008.
 190.Trachootham D, Zhou Y, Zhang H, Demizu Y, Chen Z, Pelicano H, Chiao PJ, Achanta G, Arlinghaus RB, Liu J, Huang P. Selective killing of oncogenically transformed cells through a ROS‐mediated mechanism by beta‐phenylethyl isothiocyanate. Cancer Cells 10: 241‐252, 2006.
 191.Tyurina YY, Tyurin VA, Kaynar AM, Kapralova VI, Wasserloos K, Li J, Mosher M, Wright L, Wipf P, Watkins S, Pitt BR, Kagan VE. Oxidative lipidomics of hyperoxic acute lung injury: Mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation. Am J Physiol Lung Cell Mol Physiol 299: L73‐L85, 2010.
 192.Veech RL. The therapeutic implications of ketone bodies: The effects of ketone bodies in pathological conditions: Ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids 70: 309‐319, 2004.
 193.Wada K, Ito M, Miyazawa T, Katoh H, Nawashiro H, Shima K, Chigasaki H. Repeated hyperbaric oxygen induces ischemic tolerance in gerbil hippocampus. Brain Res 740: 15‐20, 1996.
 194.Wada K, Miyazawa T, Nomura N, Tsuzuki N, Nawashiro H, Shima K. Preferential conditions for and possible mechanisms of induction of ischemic tolerance by repeated hyperbaric oxygenation in gerbil hippocampus. Neurosurgery 49: 160‐166; discussion 166‐167, 2001.
 195.Wang CH, Wu SB, Wu YT, Wei YH. Oxidative stress response elicited by mitochondrial dysfunction: Implication in the pathophysiology of aging. Exp Biol Med (Maywood) 238: 450‐460, 2013.
 196.Wang J, Yi J. Cancer cell killing via ROS: To increase or decrease, that is the question. Cancer Biol Ther 7: 1875‐1884, 2008.
 197.Wang Y, Chen D, Chen G. Hyperbaric oxygen therapy applied research in traumatic brain injury: From mechanisms to clinical investigation. Med Gas Res 4: 18, 2014.
 198.Weaver LK. UHMS: Hyperbaric Oxygen Therapy Indications. 13th Edition, Best Publishing, North Palm Beach FL, 2014.
 199.Weaver LK, Churchill S. Pulmonary edema associated with hyperbaric oxygen therapy. Chest 120: 1407‐1409, 2001.
 200.Weih M, Kallenberg K, Bergk A, Dirnagl U, Harms L, Wernecke KD, Einhaupl KM. Attenuated stroke severity after prodromal TIA: A role for ischemic tolerance in the brain? Stroke 30: 1851‐1854, 1999.
 201.Weisz G, Lavy A, Adir Y, Melamed Y, Rubin D, Eidelman S, Pollack S. Modification of in vivo and in vitro TNF‐alpha, IL‐1, and IL‐6 secretion by circulating monocytes during hyperbaric oxygen treatment in patients with perianal Crohn's disease. J Clin Immunol 17: 154‐159, 1997.
 202.Wheaton WW, Chandel NS. Hypoxia. 2. Hypoxia regulates cellular metabolism. Am J Physiol Cell Physiol 300: C385‐C393, 2011.
 203.Wolff SP, Garner A, Dean RT. Free‐radicals, lipids and protein‐degradation. Trends Biochem Sci 11: 27‐31, 1986.
 204.Wood CD, Perkins GF, Seager LD, Koerner TA. Pulmonary edema resulting from oxygen toxicity in divers. J La State Med Soc 122: 219‐221, 1970.
 205.Wright CJ, Dennery PA. Manipulation of gene expression by oxygen: A primer from bedside to bench. Pediatr Res 66: 3‐10, 2009.
 206.Xu X, Wang Z, Li Q, Xiao X, Lian Q, Xu W, Sun X, Tao H, Li R. Endothelial nitric oxide synthase expression is progressively increased in primary cerebral microvascular endothelial cells during hyperbaric oxygen exposure. Oxid Med Cell Longev 2: 7‐13, 2009.
 207.Yang Y, Bazhin AV, Werner J, Karakhanova S. Reactive oxygen species in the immune system. Int Rev Immunol 32: 249‐270, 2013.
 208.Yang Y, Zhang Y‐GG, Lin G‐AA, Xie H‐QQ, Pan H‐TT, Huang B‐QQ, Liu J‐DD, Liu H, Zhang N, Li L, Chen J‐HH. The effects of different hyperbaric oxygen manipulations in rats after traumatic brain injury. Neurosci Lett 563: 38‐43, 2014.
 209.Yee M, Vitiello PF, Roper JM, Staversky RJ, Wright TW, McGrath‐Morrow SA, Maniscalco WM, Finkelstein JN, O'Reilly MA. Type II epithelial cells are critical target for hyperoxia‐mediated impairment of postnatal lung development. Am J Physiol Lung Cell Mol Physiol 291: L1101‐L1111, 2006.
 210.Yin X, Wang X, Fan Z, Peng C, Ren Z, Huang L, Liu Z, Zhao K. Hyperbaric oxygen preconditioning attenuates myocardium ischemia‐reperfusion injury through upregulation of heme oxygenase 1 expression: PI3K/Akt/Nrf2 pathway involved. J Cardiovasc Pharmacol Ther 20: 428‐438, 2015.
 211.Yogaratnam JZ, Laden G, Guvendik L, Cowen M, Cale A, Griffin S. Hyperbaric oxygen preconditioning improves myocardial function, reduces length of intensive care stay, and limits complications post coronary artery bypass graft surgery. Cardiovasc Revasc Med 11: 8‐19, 2010.
 212.Yoshida Y, Umeno A, Shichiri M. Lipid peroxidation biomarkers for evaluating oxidative stress and assessing antioxidant capacity in vivo. J Clin Biochem Nutr 52: 9‐16, 2013.
 213.Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D'Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD. The ketone metabolite beta‐hydroxybutyrate blocks NLRP3 inflammasome‐mediated inflammatory disease. Nat Med 21: 263‐269, 2015.
 214.Yu S, Shi M, Liu C, Liu Q, Guo J, Yu S, Jiang T. Time course changes of oxidative stress and inflammation in hyperoxia‐induced acute lung injury in rats. Iran J Basic Med Sci 18: 98‐103, 2015.
 215.Yurkova IL. Free‐radical reactions of glycerolipids and sphingolipids. Russ Chem Rev 81(2): 175‐190, 2012.
 216.Zaher TE, Miller EJ, Morrow DM, Javdan M, Mantell LL. Hyperoxia‐induced signal transduction pathways in pulmonary epithelial cells. Free Radic Biol Med 42: 897‐908, 2007.
 217.Zhang Q, Chang Q, Cox RA, Gong X, Gould LJ. Hyperbaric oxygen attenuates apoptosis and decreases inflammation in an ischemic wound model. J Invest Dermatol 128: 2102‐2112, 2008.
 218.Zhang Q, Gould LJ. Hyperbaric oxygen reduces matrix metalloproteinases in ischemic wounds through a redox‐dependent mechanism. J Invest Dermatol 134: 237‐246, 2014.
 219.Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, Humala N, Thiyagarajan M, Wang J, Pasinetti GM. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci 7: 29, 2006.
 220.Zhou Z, Daugherty WP, Sun D, Levasseur JE, Altememi N, Hamm RJ, Rockswold GL, Bullock MR. Protection of mitochondrial function and improvement in cognitive recovery in rats treated with hyperbaric oxygen following lateral fluid‐percussion injury. J Neurosurg 106: 687‐694, 2007.

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Article Title: Hyperbaric Environment: Oxygen and Cellular Damage versus Protection
 

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Angela M. Poff, Dawn Kernagis, Dominic P. D'Agostino. Hyperbaric Environment: Oxygen and Cellular Damage versus Protection. Compr Physiol 2016, 7: 213-234. doi: 10.1002/cphy.c150032