Effect of Hyperoxia on the Ultrastructural Pathology of Alveolar Epithelium in Relation to Glutathione Peroxidase, Lactate Dehydrogenase Activities, and Free Radical Production in Rats,Rattus norvigicus (original) (raw)
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2013
Copyright © 2011 William J. Mach et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 O2 species (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...
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
Pediatric Research, 2020
BACKGROUND: Prolonged exposure to high oxygen concentrations in premature infants, although lifesaving, can induce lung oxidative stress and increase the risk of developing BPD, a form of chronic lung disease. The lung alveolar epithelium is damaged by sustained hyperoxia, causing oxidative stress and alveolar simplification; however, it is unclear what duration of exposure to hyperoxia negatively impacts cellular function. METHODS: Here we investigated the role of a very short exposure to hyperoxia (95% O 2 , 5% CO 2) on mitochondrial function in cultured mouse lung epithelial cells and neonatal mice. RESULTS: In epithelial cells, 4 h of hyperoxia reduced oxidative phosphorylation, respiratory complex I and IV activity, utilization of mitochondrial metabolites, and caused mitochondria to form elongated tubular networks. Cells allowed to recover in air for 24 h exhibited a persistent global reduction in fuel utilization. In addition, neonatal mice exposed to hyperoxia for only 12 h demonstrated alveolar simplification at postnatal day 14. CONCLUSION: A short exposure to hyperoxia leads to changes in lung cell mitochondrial metabolism and dynamics and has a long-term impact on alveolarization. These findings may help inform our understanding and treatment of chronic lung disease.
Journal of Clinical & Experimental Pathology, 2015
COPD are associated with an increased load on the diaphragm leading to accumulation of reactive oxygen species (ROS) and the subsequent cellular damages and death. The pathological alterations inducted by ROS in the diaphragm during oxygen breathing are not known. The purpose of the present study was to examine the effects of hyperoxia exposure (HP) on free radicals (FR) accumulation in relation to the ultrastructural pathological alterations in the diaphragm. Twenty adult male rats were randomly assigned to two groups; control (C); and hyperoxia (HP). Animals of the HP were breathing 100% O 2 for 72 hr continuously. Both serum and diaphragm tissue supernatant analysis showed significantly higher (p<0.05) FR in HP group, as compared with control group. Ultrastructure examinations showed that HP resulted in variety of pathological alterations in the mitochondria and endoplasmic reticulum that were associated with disarrangement of myofibrils, loss of I-banding for myosin, focal myolysis of the myofilaments, complete fragmentation of myosin, tearing of myofilamments from Z plates and tearing of the endothelial cell of the interstitial blood capillaries. Based on the results of the present study, it can be concluded that hyperoxia-induced acceleration ROS formation damaged the contractile apparatuses of the diaphragm and related endomembrane proteins that could involve intracellular calcium channels proteins.
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...
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
Interactions of Oxygen Radicals with Airway Epithelium
Environmental Health Perspectives, 1994
Reactive oxygen species (ROS) have been implicated in the pathogenesis of numerous disease processes. Epithelial cells lining the respiratory airways are uniquely vulnerable regarding potential for oxidative damage due to their potential for exposure to both endogenous (e.g., mitochondrial respiration, phagocytic respiratory burst, cellular oxidases) and exogenous (e.g., air pollutants, xenobiotics, catalase negative organisms) oxidants. Airway epithelial cells use several nonenzymatic and enzymatic antioxidant mechanisms to protect against oxidative insult. Nonenzymatic defenses include certain vitamins and low molecular weight compounds such as thiols. The enzymes superoxide dismutase, catalase, and glutatione peroxidase are major sources of antioxidant protection. Other materials associated with airway epithelium such as mucus, epithelial lining fluid, and even the basement membrane/extracellular matrix may have protective actions as well. When the normal balance between oxidants and antioxidants is upset, oxidant stress ensues and subsequent epithelial cell alterations or damage may be a critical component in the pathogenesis of several respiratory diseases. Oxidant stress may profoundly alter lung physiology including pulmonary function (e.g., forced expiratory volumes, flow rates, and maximal inspiratory capacity), mucociliary activity, and airway reactivity. ROS may induce airway inflammation; the inflammatory process may serve as an additional source of ROS in airways and provoke the pathophysiologic responses described. On a more fundamental level, cellular mechanisms in the pathogenesis of ROS may involve activation of intracellular signaling enzymes including phospholipases and protein kinases stimulating the release of inflammatory lipids and cytokines. Respiratory epithelium may be intimately involved in defense against, and pathophysiologic changes invoked by, ROS. -Environ Health Perspect 1 02(Suppl 1 0): 85-90 (1994)
Saudi journal of biological sciences, 2010
Oxygen therapy has been widely used in lung injury (Li), adult respiraotory syndrome (ARDS) and inflammatory lung diseases as well as in mechanical ventilation in intensive care units. Exposure to hyperoxia is known to induct the production of reactive oxygen species (ROS) by mitochondria. Despite decades of research, the role of hyperoxia training in oxidative stress and ROS formation in the lungs is not known. The purpose of this study was to examine the effects of periodic-hyperoxia training on biological antioxidants (BAP) and lactate dehydrogenase (LDH) activities and free radicals (FR) production. Thirty adult male rats, matched with age and body weigh, were randomly assigned to three groups. The first group served as control (C) and the second (HP) was exposed to hyperoxia for 48. Animals in the third group (HP-T) were trained on hyperoxia for 1.5 h daily for three weeks. Following the exposure period for each group animals were sacrificed and lungs tissues were homogenized f...
Mitochondrial thiol status in the liver is altered by exposure to hyperoxia
Toxicology Letters, 2001
Patients with poorly functioning lungs often require treatment with high concentrations of supplemental oxygen, which, although often necessary to sustain life, can cause lung injury. The mechanisms responsible for hyperoxic lung injury have been investigated intensely and most probably involve oxidant stress responses, but the details are not well understood. In the present studies, we exposed adult male C57/Bl6 mice to \ 95% O 2 for up to 72 h and obtained lung and liver samples for assessment of lung injury, measurements of tissue concentrations of coenzyme A (CoASH) and the corresponding mixed disulfide with glutathione (CoASSG), as possible biomarkers of intramitochondrial thiol redox status. Subcellular fractions were prepared from both tissues for determination of glutathione reductase (GR) activities. Lung injury in the hyperoxic mice was demonstrated by increases in lung weight to body weight ratios at 48 h and by increases in bronchoalveolar lavage protein concentrations at 72 h. Lung CoASH concentrations declined in the hyperoxic mice, but CoASSG concentrations were not increased nor were CoASH/CoASSG ratios decreased, as would be expected for an oxidant shift in mitochondrial thiol-disulfide status. Interestingly, CoASSG concentrations increased (from 6.72 90.54 to 14.10 9 1.10 nmol/g of liver in air-breathing controls and 72 h of hyperoxia, respectively, PB0.05), and CoASH/CoASSG ratios decreased in the livers of mice exposed to hyperoxia. Some apparent effects of duration of hyperoxia on GR activities in lung or liver cytosolic, mitochondrial, or nuclear fractions were observed, but the changes were not consistent or progressive. Yields of isolated hepatic nuclear protein were decreased in the hyperoxic mice within 24 h of exposure, and by 72 h of hyperoxia, protein recoveries in purified nuclear fractions had declined from 41.8 to 14.8 mg of protein/g animal body weight. Concentrations of 10-formyltetrahydrafolate dehydrogenase were diminished in hepatic mitochondria of hyperoxic mice. A second protein in hepatic mitochondria of : 25 kDa showed apparent decreases in thiol content, as determined by fluorescence intensities of monobromobimane derivatives separated by SDS-PAGE. The mechanisms responsible for the observed effects and the possible implications for the adverse effects of hyperoxic therapies are not known and need to be investigated.