Role of Iron in Hyperoxia-Induced Lung Injury: One Step Forward in
Background: An increased oxidative stress in patients under treatment with high concentrations of oxygen (hyperoxia) is considered to be one of the major mechanisms of lung injury. Between different mediators, transition metal ions especially iron, by generation of very reactive free radicals play an important role in oxidative stress process. Disruption of normal iron hemostasis has been reported in hyperoxic conditions. So we hypothesized that chelation of iron can reduce hyperoxia- induced lung injury.
Methods: Mechanically ventilated patients, who received oxygen with FiO > 0.5 for at least 3 days, underwent bronchoscopy at baseline and 72 hours thereafter. Data from external control cases were collected prospectively to provide a comparative reference group.Iron and Iron-related proteins were measured in lavage fluid and plasma.
Results: In 24 patients and in comparison with the results of previous study, Iron concentration decreased significantly in lavage fluid (P<0.001). Reduction of ferritin was not significant in lavage fluid (P: 0.7).Transferrin decreased significantly in plasma (P: 0.01). Acute Physiology And Chronic Health Evaluation (APACHE) II (P: 0.006) score decreased significantly after 7 days of follow-up.
Conclusion: Deferasirox did not change Iron and Iron-related protein in hyperoxic condition and it just only could be considered along with other supportive measures for better toleration of oxygen therapy.
Patel d, Goel A, Agrawal SB, Gary P, Lakhani K. Oxygen toxicity. JIAMC 2003; 4(3):234-7.
Fink M. Role of reactive oxygen and nitrogen species in ARDS. Curr Opin Crit Care 2002; 8(1):6-11.
Chow Ch, Abreu M, Suzuki T, Downey G. Oxidative stress and acute lung injury. Am J Respir Cell Mol Biol 2003; 29:427-31.
Lung J, McArdle Ph, O’reilly Ph, Matalon S. Oxidant-antioxidant balance in acute lung injury. Chest 2002; 122:S314-S320.
Nash G, Blennerhassett J, Pontoppidan H. Pulmonary lesion associated with oxygen therapy and artificial ventilation. N Engl J Med 1967; 276:368-74.
Zaher T, Miller E, Morrow D, Javdan M, Mantell L. Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells. Free Radic Biol Med 2007; 42(7):897-908.
Altemeir W, Sinclair S. Hyperoxia in the intensive care unit: Why more is not always better. Curr Opin Crit Care 2007; 13:73-8.
McCord JM. Iron, free radicals and oxidative injury. Semin Hematol 1998; 35(1):5-12.
Emerit J, Beaumont C, Trivin F. Iron metabolism, free radicals and oxidative injury. Biomed Pharmacother 2001; 55:333-9.
Turi J, Yang F, Garrick M, Piantadosi C, Ghio A. The iron cycle and oxidative stress in the lung. Free Radic Biol Med 2004; 36(7):850-7.
Legan A, Melley D, Evans T, Quinlan G. Pathogenesis of the systemic inflammatory syndrome and acute lung injury: role of iron mobilization and decompartmentalization. Am J Physiol Lung Cell Mol Physiol 2008; 294:L161-L174.
Mateos F, Brock J, Perez-Arellano J. Iron metabolism in the lower respiratory tract.Thorax 1998; 53:594-600.
Drossos G, Lazou A, Panagopoulos P, Westaby S. Deferoxamine cardioplegia reduces superoxide radical production in human myocardium. Ann Thorac Surg 1995; 59:169-72.
Nakamura T, Keep R, Hua Y, Schallert T, Hoff J, Xi G. Deferoxamineinduced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage. Neurosurg Focus 2003; 15(4):1-7.
Paraskevaidis L, Lliodromitis EK, Vlahakos D, Tsiapras D, Nikolaidis A, Marathias A, et al. Deferoxamine infusion during coronary artery bypass grafting ameliorates lipid peroxidation and protects the myocardium against reperfusion injury: immediate and long-term significance. Eur Heart J 2005; 26:263-70.
Prass K, Ruscher K, Karsch M, Isaev N, Megow D, Priller J, et al. Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro. J Cerebral Blood flow and Metabolism 2002; 22: 520-5.
Mousavi S, Mojtahedzadeh M, Abdollahi M. Place of iron chelators like Desferrioxamine and Deferasirox in management of hyperoxia-induced lung injury: A systematic review. Int J pharmacol 2010; 6:1-12.
Stumpf J. Deferasirox. Am J Health-syst Pharm 2007; 64:606-16.
Vanorden H, Hagemann T. Deferasirox.An oral agent for chronic iron overload. Ann Phamacother 2006; 40:1110-7.
Pantarulo S. Iron, oxidative stress and human health. Mol Aspects Med 2005; 26:299-312.
Lamb N, Gutteridge J, Baker C, Evans T, Quinlan G. Oxidant damage to proteins of bronchoalveolar lavage fluid in patients with ARDS. Crit Care Med 1999; 27(9):1738-44.
Sinclair S, Altemeir W, Matute-Bello G, Chi E. Augmented lung injury due to interaction between hyperoxia and mechanical ventilation. Crit Care Med 2004; 32:2496-501.
Ghio A, Carter J, Richards J, Richer L, Grissom C, Elstad M. Iron and iron related protein in the lower respiratory tract of patients with ARDS. Crit Care Med 2003; 31(2):395-400.
D’angio CT, Lomonaco MB, Chaudhry SA, Paxhia A, Ryan RM. Discordant pulmonary proinflammatory cytokines expression during acute hyperoxia in the newborn rabbit. Exp Lung Res 1999; 25:443-65.
Bailey T, Martin E, Zhao L, Veldhuizen R. High oxygen concetrations predispose mouse lungs to the deleterious effects of high stretch ventilation. J App Physiol 2003; 94:975-82.
Baleeiro C, Wilcoxen S, Morris S, Standiford Th, Paine R. Sublethal hyperoxia impaires pulmonary innate immunity. J Immunol 2003; 171:955-63.
Tateda K, Deng J, Moore Th, Neustead M, Paine R, Kobayashi N, et al. Hyperoxia mediates Acute lung injury and increased lethality in Murine Legionella pneumonia:The role of apoptosis. J Immunol 2003; 170: 4209-16.
Yang F, Coalson J, Bobb H, Carter J, Banu J, Ghio A. Resistance of hypotransferrinemic mice to hyperoxia-induced lung injury. Am J Physiol Lung Cell Mol Physiol 1999; 277:1214- 23.
Kontoghioghes GJ, Kolnagou A, Peng CT, Shah SV, Aessopos A. Safety issues of iron chelation therapy in patients with normal range iron stores including thalassaemia, neurodegenerative, renal and infectious diseases. Expert Opin Drug Saf 2010; 9(2):201-6.
Hershko Ch. Iron chelators in medicine. Mol Aspects Med 1992; 45: 276-81.
Ritter C, Dacunha AA, Isaber C, Adrades M, Reinke A, Lucchiari N, et al. Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharideinduced acute lung injury in the rat. Crit Care Med 2006; 34(2):471-7.
Lalonde C, Ikegani K, Demling R. Aerosolized deferoxamine prevents lung and systemic injury caused by smoke inhalation. J App Physiol 1994; 77(5):2057-64.
Pinho R, Silveria P, Silva L, Streck E, Dal-Pizzol F, Moreira J. N-acetylcysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure. Environ Res 2005; 99(3):355-60.
Mousavi S, Abdollahi M, Ahmadi A, Najafi A, Pazoki M, Hadjibabaei M, et al. The dilemma of hyperoxia following positive pressure mechanical ventilation: role of iron and the benefit of iron chelation with deferasirox. Eur Rev Med Pharmacol Sci 2011; 15(10):1141-48.
Copyright (c) 2015 Journal of Pharmaceutical Care
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.