title: Role of heme in bromine-induced lung injury.
abstract: Bromine (Br2 ) gas inhalation poses an environmental and occupational hazard resulting in high morbidity and mortality. In this review, we underline the acute lung pathology (within 24 h of exposure) and potential therapeutic interventions that may be utilized to mitigate Br2 -induced human toxicity. We discuss our latest published data, which suggest that an increase in heme-dependent tissue injury underlies the pathogenesis of Br2 toxicity. Our study was based on previous findings that demonstrated that Br2 upregulates the heme-degrading enzyme heme oxygenase-1 (HO-1), which converts toxic heme into bilverdin. Interestingly, following Br2 inhalation, heme levels were indeed elevated in bronchoalveolar lavage fluid, plasma, and whole lung tissue in C57BL/6 mice. High heme levels correlated with increased lung oxidative stress, lung inflammation, respiratory acidosis, lung edema, higher airway resistance, and mortality. However, therapeutic reduction of heme levels, by either scavenging with hemopexin or degradation by HO-1, improved lung function and survival. Therefore, heme attenuation may prove a useful adjuvant therapy to treat patients after Br2 exposure.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine and Division of Molecular and Translational Biomedicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Adam
authors.initials: A
authors.lastname: Lam
authors.affiliation: Department of Anesthesiology and Perioperative Medicine and Division of Molecular and Translational Biomedicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Nilam
authors.initials: N
authors.lastname: Vetal
authors.affiliation: Department of Anesthesiology and Perioperative Medicine and Division of Molecular and Translational Biomedicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Sadis
authors.initials: S
authors.lastname: Matalon
authors.affiliation: Department of Anesthesiology and Perioperative Medicine and Division of Molecular and Translational Biomedicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Aggarwal
mesh_terms: D000818:Animals; D001966:Bromine / Q000633:toxicity*; D006418:Heme / Q000494:pharmacology*; D006801:Humans; D019570:Inhalation Exposure / Q000032:analysis; D055370:Lung Injury / Q000139:chemically induced* / Q000473:pathology; D008954:Models, Biological; D011634:Public Health
chemical_list: D006418:Heme; D001966:Bromine
keywords: bromine; heme; heme oxygenase; hemopexin; lung injury