title: Gene expression profile of oxidative stress and antioxidant defense in lung tissue of patients exposed to sulfur mustard.
abstract: Sulfur mustard (SM) is a potent alkylating agent that targets several organs, especially lung tissue. Although pathological effects of SM on mustard lung have been widely considered, molecular and cellular mechanisms for these pathologies are poorly understood. We investigated changes in expression of genes related to oxidative stress (OS) and antioxidant defense caused by SM in lung tissue of patients. We performed gene expression profiling of OS and antioxidant defense in lung tissue samples from healthy controls (n=5) and SM-exposed patients (n=6). Changes in gene expression were measured using a 96-well RT(2) Profiler ™PCR Array: Human Oxidative Stress and Antioxidant Defense, which arrayed 84 genes functionally involved in cellular OS response. 47 (55.95%) genes were found to be significantly upregulated in patients with mustard lung compared with controls (p<0.05), whereas 7 (8.33%) genes were significantly downregulated (p<0.05). Among the most upregulated genes were OS responsive-1 (OXSR1), forkhead box M1 (FOXM1), and glutathione peroxidase-2 (GPX2), while metallothionein-3 (MT3) and glutathione reductase (GSR) were the most downregulated genes. Expression of hypoxia-induced genes (CYGB and MB), antioxidants and reactive oxygen species (ROS)-producing genes were significantly altered, suggesting an increased oxidative damage in mustard lungs. Mustard lungs were characterized by hypoxia, massive production of ROS, OS, disruption of epithelial cells, surfactant dysfunction, as well as increased risk of lung cancer and pulmonary fibrosis. Oxidative stress induced by ROS is the major mechanism for direct effect of SM exposure on respiratory system. Antioxidant treatment may improve the main features of mustard lungs.
authors.affiliation: Chemical Injuries Research Center, Baqiatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Eisa
authors.initials: E
authors.lastname: Tahmasbpour
authors.affiliation: Chemical Injuries Research Center, Baqiatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ghanei
authors.affiliation: Chemical Injuries Research Center, Baqiatallah University of Medical Sciences, Tehran, Iran; Department of Pulmonology, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Qazvini
authors.affiliation: Chemical Injuries Research Center, Baqiatallah University of Medical Sciences, Tehran, Iran; Department of Pulmonology, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Ensieh
authors.initials: E
authors.lastname: Vahedi
authors.affiliation: Chemical Injuries Research Center, Baqiatallah University of Medical Sciences, Tehran, Iran. Electronic address: yunespanahi@yahoo.com.
authors.forename: Yunes
authors.initials: Y
authors.lastname: Panahi
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D002619:Chemical Warfare Agents / Q000506:poisoning; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D000860:Hypoxia; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009151:Mustard Gas / Q000506:poisoning*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D002619:Chemical Warfare Agents; D017382:Reactive Oxygen Species; D009151:Mustard Gas
keywords: Antioxidants; Gene expression; Lung tissue; Oxidative stress; Reactive oxygen species; Sulfur mustard