doi:10.1155/2011/260482 Review Article Consequences of Hyperoxia and the Toxicity of Oxygen in the Lung (original) (raw)

Consequences of Hyperoxia and the Toxicity of Oxygen in the Lung

Nursing Research and Practice, 2011

Oxygen (O2) is life essential but as a drug has a maximum positive biological benefit and accompanying toxicity effects. Oxygen is therapeutic for treatment of hypoxemia and hypoxia associated with many pathological processes. Pathophysiological processes are associated with increased levels of hyperoxia-induced reactive O2species (ROS) which may readily react with surrounding biological tissues, damaging lipids, proteins, and nucleic acids. Protective antioxidant defenses can become overwhelmed with ROS leading to oxidative stress. Activated alveolar capillary endothelium is characterized by increased adhesiveness causing accumulation of cell populations such as neutrophils, which are a source of ROS. Increased levels of ROS cause hyperpermeability, coagulopathy, and collagen deposition as well as other irreversible changes occurring within the alveolar space. In hyperoxia, multiple signaling pathways determine the pulmonary cellular response: apoptosis, necrosis, or repair. Unders...

Hyperoxia-induced Cell Death in the Lung-the Correlation of Apoptosis, Necrosis, and Inflammation

Annals of The New York Academy of Sciences, 2006

A BSTRACT : Prolonged exposure to hyperoxia causes tissue damage in many organs and tissues. Since the entire surface area of lung epithelium is directly exposed to O 2 and other inhaled agents, hyperoxia leads to the development of both acute and chronic lung injuries.These pathologic changes in the lung can also be seen in acute lung injury (ALI) in response to other agents. Simple strategies to mitigate hyperoxia-induced ALI might not be effective by virtue of merely reducing or augmenting the extent of apoptosis of pulmonary cells. Identification of the specific cell types undergoing apoptosis and further understanding of the precise timing of the onset of apoptosis may be necessary in order to gain a greater understanding of the connection between apoptosis and tolerance to hyperoxia and ALI. Attention should also be focused on other forms of non-apoptotic programmed cell death.

Hyperoxia and Lungs: What We Have Learned From Animal Models

Frontiers in Medicine, 2021

Although oxygen (O2) is essential for aerobic life, it can also be an important source of cellular damage. Supra-physiological levels of O2 determine toxicity due to exacerbated reactive oxygen species (ROS) production, impairing the homeostatic balance of several cellular processes. Furthermore, injured cells activate inflammation cascades, amplifying the tissue damage. The lung is the first (but not the only) organ affected by this condition. Critically ill patients are often exposed to several insults, such as mechanical ventilation, infections, hypo-perfusion, systemic inflammation, and drug toxicity. In this scenario, it is not easy to dissect the effect of oxygen toxicity. Translational investigations with animal models are essential to explore injuring stimuli in controlled experimental conditions, and are milestones in understanding pathological mechanisms and developing therapeutic strategies. Animal models can resemble what happens in critical care or anesthesia patients u...

Hyperoxia causes angiopoietin 2–mediated acute lung injury and necrotic cell death

Nature Medicine, 2006

The angiogenic growth factor angiopoietin 2 (Ang2) destabilizes blood vessels, enhances vascular leak and induces vascular regression and endothelial cell apoptosis. We considered that Ang2 might be important in hyperoxic acute lung injury (ALI). Here we have characterized the responses in lungs induced by hyperoxia in wild-type and Ang2 -/mice or those given either recombinant Ang2 or short interfering RNA (siRNA) targeted to Ang2. During hyperoxia Ang2 expression is induced in lung epithelial cells, while hyperoxia-induced oxidant injury, cell death, inflammation, permeability alterations and mortality are ameliorated in Ang2 -/and siRNA-treated mice. Hyperoxia induces and activates the extrinsic and mitochondrial cell death pathways and activates initiator and effector caspases through Ang2-dependent pathways in vivo. Ang2 increases inflammation and cell death during hyperoxia in vivo and stimulates epithelial necrosis in hyperoxia in vitro. Ang2 in plasma and alveolar edema fluid is increased in adults with ALI and pulmonary edema. Tracheal Ang2 is also increased in neonates that develop bronchopulmonary dysplasia. Ang2 is thus a mediator of epithelial necrosis with an important role in hyperoxic ALI and pulmonary edema.

Oxygen radicals and lung injury

Acta Anaesthesiologica Scandinavica, 1991

Kistler GS, Caldwell PRB, Weibel ER. Development of fine structural damage to alveolar and capillary lining cells in oxygen-poisoned lungs. J Cell Biol1967; 32:605-27 6 Bonikos DS, Bensch KG, Northway WH Jr. Oxygen tolicity in the newborn. The effect of chronic continuous 1()()CI, oxygen exposure on the lungs of newborn mice. Am J Pathol 1976; 85:623-35 7 ICapanci ~ Weibel ER, Kaplan HP, Robinson FR. Pathogenesis and reversibility of the pulmonary lesions in oxygen toxicity in monkeys. n. Ultrastructural and morphomebic studies. Lab

Dissociation between alveolar transmigration of neutrophils and lung injury in hyperoxia

AJP: Lung Cellular and Molecular Physiology, 2006

The objective of this study was to quantitatively assess changes in cell adhesion molecule (CAM) expression on the pulmonary endothelial surface during hyperoxia and to assess the functional significance of those changes on cellular trafficking and development of oxygen-induced lung injury. Mice were placed in >95% O2 for 0–72 h, and pulmonary injury and neutrophil (PMN) sequestration were assessed. Specific pulmonary CAM expression was quantified with a dual-radiolabeled MAb technique. To test the role of CAMs in PMN trafficking during hyperoxia, blocking MAbs to murine P-selectin, ICAM-1, or platelet-endothelial cell adhesion molecule-1 (PECAM-1) were injected in wild-type mice. Mice genetically deficient in these CAMs and PMN-depleted mice were also evaluated. PMN sequestration occurred within 8 h of hyperoxia, although alveolar emigration occurred later (between 48 and 72 h), coincident with rapid escalation of the lung injury. Hyperoxia significantly increased pulmonary upta...

Time course of inflammation, oxidative stress and tissue damage induced by hyperoxia in mouse lungs

International Journal of Experimental Pathology, 2012

Acute lung injury (ALI) affects a large number of patients worldwide, with reported mortality rates of 35-40% (Rubenfeld & Herridge 2007). Many patients with ALI require oxygen supplementation to maintain adequate tissue oxygenation, leading to hyperoxia (Fisher & Beers 2008). However, exposure to hyperoxia can have pathological effects, such as lung inflammation and oedema accompanied by epithelial and endothelial cell death, suggesting that oxygen supplementation, although necessary, may potentially perpetuate or exacerbate ALI (Bhandari et al. 2006; Bhandari 2008). Paradoxically, hyperoxia may cause ALI and damage to components of the extracellular matrix (Murray et al. 2008). Moreover, hyperoxia has been linked to the production of reactive oxygen species (ROS) and subsequent oxida-tive stress (Huang et al. 2009). Reactive oxygen species are important mediators in ALI, attacking biological molecules and causing lipid peroxidation, protein oxidation and DNA breakage (Papaiahgari et al. 2006). Under physiological conditions, living organisms maintain a balance between the formation and removal of ROS (Owuor & Kong 2002). The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase and non-enzymatic antioxidants, such as a-tocopherol, vitamin-C, carotenoids and the glutathione system, all prevent the formation of toxic levels of ROS. Oxidative stress occurs when the generation of ROS in a system exceeds the system's capacity to neutralize and eliminate the ROS (Sies 1997

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

Free Radical Biology and Medicine, 2007

Mechanical ventilation with hyperoxia is necessary to treat critically ill patients. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), which can cause acute inflammatory lung injury. One of the major effects of hyperoxia is the injury and death of pulmonary epithelium, which is accompanied by increased levels of pulmonary proinflammatory cytokines and excessive leukocyte infiltration. A thorough understanding of the signaling pathways leading to pulmonary epithelial cell injury/death may provide some insights into the pathogenesis of hyperoxia-induced acute inflammatory lung injury. This review focuses on epithelial responses to hyperoxia and some of the major factors regulating pathways to epithelial cell injury/death, and proinflammatory responses upon exposure to hyperoxia. We discuss in detail some of the most interesting players, such as, NF-κB, that can modulate both proinflammatory responses and cell injury/death of lung epithelial cells. A better appreciation for the functions of these factors will no doubt help us to delineate the pathways to hyperoxic cell death and proinflammatory responses.

Effects of hyperoxic exposure on signal transduction pathways in the lung

Respiratory Physiology & Neurobiology, 2015

Exposure to supraphysiological concentrations of oxygen is often applied in clinical practice to enhance oxygenation in acute or chronic lung injury. However, hyperoxic exposure is associated with increased reactive oxygen species production, which can be toxic to pulmonary endothelial and alveolar epithelial cells. Oxidative stress activates the pathways of the mitogen-activated protein kinases family: extracellular signal-regulated kinase (ERK1/2), C-Jun-terminal protein kinase (JNK1/2), and p38 kinase. Several studies have suggested that ERK activation in lung cells has a protective effect in response to hyperoxia, through stimulation of DNA repair and antioxidant mechanisms, and prolonged cell survival. Conversely, JNK1/2 and p38 kinase have been most frequently reported to have roles in induction of apoptotic responses. Moreover, exogenous factors, such as ATP, retinoic acid, substance P, thioredoxin, inosine and laminin, can have cytoprotective effects against hyperoxia-induced cell damage, through promotion of ERK activation and/or limiting JNK and p38 involvement.