{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:48Z","timestamp":1787029068215,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council, Canada","doi-asserted-by":"publisher","award":["NSERC CRD 488647-2015"],"award-info":[{"award-number":["NSERC CRD 488647-2015"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Iron plays a critical role in the immune response to inflammation and infection due to its role in the catalysis of reactive oxygen species (ROS) through the Haber-Weiss and Fenton reactions. However, ROS overproduction can be harmful and damage healthy cells. Therefore, iron chelation represents an innovative pharmacological approach to limit excess ROS formation and the related pro-inflammatory mediator cascades. The present study was designed to investigate the impact of the iron chelator, DIBI, in an experimental model of LPS-induced acute lung injury (ALI). DIBI was administered intraperitoneally in the early and later stages of lung inflammation as determined by histopathological evaluation. We found that lung tissues showed significant injury, as well as increased NF-\u03baB p65 activation and significantly elevated levels of various inflammatory mediators (LIX, CXCL2, CCL5, CXCL10, IL-1\ud835\udefd, IL-6) 4 h post ALI induction by LPS. Mice treated with DIBI (80 mg\/kg) in the early stages (0 to 2 h) after LPS administration demonstrated a significant reduction of the histopathological damage score, reduced levels of NF-\u03baB p65 activation, and reduced levels of inflammatory mediators. Intravital microscopy of the pulmonary microcirculation also showed a reduced number of adhering leukocytes and improved capillary perfusion with DIBI administration. Our findings support the conclusion that the iron chelator, DIBI, has beneficial anti-inflammatory effects in experimental ALI.<\/jats:p>","DOI":"10.3390\/molecules27134036","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T22:43:00Z","timestamp":1656024180000},"page":"4036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Anti-Inflammatory Effects of the Iron Chelator, DIBI, in Experimental Acute Lung Injury"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-9168","authenticated-orcid":false,"given":"Christian","family":"Lehmann","sequence":"first","affiliation":[{"name":"Department of Physiology & Biophysics, Dalhousie University, Halifax, NS B3H 1X5, Canada"},{"name":"Department of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 1X5, Canada"},{"name":"Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazli","family":"Alizadeh-Tabrizi","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Dalhousie University, Halifax, NS B3H 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9670-6192","authenticated-orcid":false,"given":"Stefan","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Dalhousie University, Halifax, NS B3H 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sufyan","family":"Faridi","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Euodia","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Holbein","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Dalhousie University, Halifax, NS B3H 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS B3H 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8339-1363","authenticated-orcid":false,"given":"Valerie","family":"Chappe","sequence":"additional","affiliation":[{"name":"Department of Physiology & Biophysics, Dalhousie University, Halifax, NS B3H 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/bjaed\/mkx002","article-title":"Acute Respiratory Distress Syndrome","volume":"17","author":"McCormack","year":"2017","journal-title":"BJA Educ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1136\/thoraxjnl-2015-207461","article-title":"The pulmonary endothelium in acute respiratory distress syndrome: Insights and therapeutic opportunities","volume":"71","author":"Millar","year":"2016","journal-title":"Thorax"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7264383","DOI":"10.1155\/2019\/7264383","article-title":"Intranasal Application of Budesonide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Nucleotide-Binding Oligomerization Domain-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation in Mice","volume":"2019","author":"Dong","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102573","DOI":"10.1016\/j.autrev.2020.102573","article-title":"COVID-19 Gone Bad: A New Character in the Spectrum of the Hyperferritinemic Syndrome?","volume":"19","author":"Colafrancesco","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111228","DOI":"10.1016\/j.biopha.2021.111228","article-title":"The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators","volume":"136","author":"Habib","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"L379","DOI":"10.1152\/ajplung.00010.2008","article-title":"Animal Models of Acute Lung Injury","volume":"295","author":"Frevert","year":"2008","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000315915","article-title":"Endotoxins and Other Sepsis Triggers","volume":"Volume 167","author":"Opal","year":"2010","journal-title":"Endotoxemia and Endotoxin Shock"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e66","DOI":"10.1038\/emm.2013.97","article-title":"Recognition of lipopolysaccharide pattern by TLR4 complexes","volume":"45","author":"Park","year":"2013","journal-title":"Exp. Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3389\/fphys.2020.00036","article-title":"Molecular Dynamics of Lipopolysaccharide-Induced Lung Injury in Rodents","volume":"11","author":"Domscheit","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/35021228","article-title":"Toll-like receptors in the induction of the innate immune response","volume":"406","author":"Aderem","year":"2000","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3233\/CH-179205","article-title":"Anti-inflammatory effects of a novel iron chelator, DIBI, in experimental sepsis","volume":"67","author":"Thorburn","year":"2017","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3233\/CH-189109","article-title":"DIBI, a polymeric hydroxypyridinone iron chelator, reduces ocular inflammation in local and systemic endotoxin-induced uveitis","volume":"69","author":"Arora","year":"2018","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3233\/CH-201078","article-title":"Anti-inflammatory iron chelator, DIBI, reduces leukocyte-endothelial adhesion and clinical symptoms of LPS-induced interstitial cystitis in mice","volume":"79","author":"Hagn","year":"2021","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"516740","DOI":"10.1155\/2015\/516740","article-title":"The Utility of Iron Chelators in the Management of Inflammatory Disorders","volume":"2015","author":"Lehmann","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3233\/CH-209207","article-title":"The novel iron chelator, DIBI, attenuates inflammation and improves outcome in colon ascendens stent peritonitis-induced experimental sepsis","volume":"76","author":"Fokam","year":"2020","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0741-8329(03)00100-9","article-title":"Iron-dependent activation of NF-\u03baB in Kupffer cells: A priming mechanism for alcoholic liver disease","volume":"30","author":"Xiong","year":"2003","journal-title":"Alcohol"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s10534-020-00253-1","article-title":"Enhanced Fe3+ binding through cooperativity of 3-hydroxypyridin-4-one groups within a linear co-polymer: Wrapping effect leading to superior antimicrobial activity","volume":"33","author":"Ang","year":"2020","journal-title":"BioMetals"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"G1355","DOI":"10.1152\/ajpgi.1997.272.6.G1355","article-title":"Role of iron in NF-kappa B activation and cytokine gene expression by rat hepatic macrophages","volume":"272","author":"Lin","year":"1997","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3233\/JCB-209011","article-title":"DIBI, a novel polymeric iron chelator modulates IL-6 and IL-8 secretion from Cystic Fibrosis airway epithelial cells in response to endotoxin induction","volume":"6","author":"Aali","year":"2020","journal-title":"J. Cell. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1161\/01.ATV.0000245820.34238.da","article-title":"Iron Chelation Inhibits NF-\u039aB\u2013Mediated Adhesion Molecule Expression by Inhibiting P22phox Protein Expression and NADPH Oxidase Activity","volume":"26","author":"Li","year":"2006","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.3324\/haematol.2009.016824","article-title":"Deferasirox Is a Powerful NF-\u039aB Inhibitor in Myelodysplastic Cells and in Leukemia Cell Lines Acting Independently from Cell Iron Deprivation by Chelation and Reactive Oxygen Species Scavenging","volume":"95","author":"Messa","year":"2010","journal-title":"Haematologica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"300060520951015","DOI":"10.1177\/0300060520951015","article-title":"Deferasirox, an iron-chelating agent, alleviates acute lung inflammation by inhibiting neutrophil activation and extracellular trap formation","volume":"48","author":"Kono","year":"2020","journal-title":"J. Int. Med Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1002\/jat.3773","article-title":"Role of iron and oxidative stress in the exacerbation of allergic inflammation in murine lungs caused by urban particulate matter <2.5 \u00b5m and desert dust","volume":"39","author":"He","year":"2019","journal-title":"J. Appl. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0022-2143(98)90128-7","article-title":"Differential regulation of human alveolar macrophage-derived interleukin-1\u03b2 and tumor necrosis factor-\u03b1 by iron","volume":"132","author":"Blumer","year":"1998","journal-title":"J. Lab. Clin. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jss.2015.07.001","article-title":"Anti-inflammatory and anti-bacterial effects of iron chelation in experimental sepsis","volume":"200","author":"Islam","year":"2016","journal-title":"J. Surg. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lehmann, C., Aali, M., Zhou, J., and Holbein, B. (2021). Comparison of Treatment Effects of Different Iron Chelators in Experimental Models of Sepsis. Life, 11.","DOI":"10.3390\/life11010057"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"H1613","DOI":"10.1152\/ajpheart.2000.278.5.H1613","article-title":"Heme oxygenase modulates selectin expression in different regional vascular beds","volume":"278","author":"Vachharajani","year":"2000","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"H474","DOI":"10.1152\/ajpheart.00655.2005","article-title":"Macromolecule permeability of in situ and excised rodent skeletal muscle arterioles and venules","volume":"290","author":"Sarelius","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_29","first-page":"170","article-title":"Mouse Models of Human Disease: An Evolutionary Perspective","volume":"2016","author":"Perlman","year":"2016","journal-title":"Evol. Med. Public Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of mice and not men: Differences between mouse and human immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"621","DOI":"10.4049\/jimmunol.177.1.621","article-title":"Gender Differences in Murine Airway Responsiveness and Lipopolysaccharide-Induced Inflammation","volume":"177","author":"Card","year":"2006","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"17","DOI":"10.17480\/psk.2021.65.1.17","article-title":"Strain, Age, and Gender Differences in Response to Lipopolysaccharide (LPS) Animal Model of Sepsis in Mice","volume":"65","author":"Gahima","year":"2021","journal-title":"Yakhak Hoeji"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/aor.13812","article-title":"Hyperferritinemia in Patients with COVID-19: An Opportunity for Iron Chelation?","volume":"45","author":"Vlahakos","year":"2021","journal-title":"Artif. Organs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s12026-020-09145-5","article-title":"COVID-19 as part of the hyperferritinemic syndromes: The role of iron depletion therapy","volume":"68","author":"Perricone","year":"2020","journal-title":"Immunol. Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/13\/4036\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:38:24Z","timestamp":1760139504000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/13\/4036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,23]]},"references-count":34,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["molecules27134036"],"URL":"https:\/\/doi.org\/10.3390\/molecules27134036","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,23]]}}}