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Gene expression profile of oxidative stress and antioxidant defense in lung tissue of patients exposed to sulfur mustard

TitleGene expression profile of oxidative stress and antioxidant defense in lung tissue of patients exposed to sulfur mustard
Publication TypeJournal Article
Year of Publication2016
AuthorsTahmasbpour E., Ghanei M., Qazvini A., Vahedi E., Panahi Y.
JournalMutat Res Genet Toxicol Environ Mutagen
Volume800-801
Pagination12-21
Date PublishedApr
ISBN Number1383-5718 (Linking)
Accession Number27085470
KeywordsAdult, Aged, ANTIOXIDANTS, Antioxidants/*metabolism, Chemical Warfare Agents/poisoning, Epithelium/drug effects/metabolism/pathology, Gene Expression, Gene Expression Profiling/methods, Gene Regulatory Networks/drug effects, Humans, Hypoxia, Lung tissue, Lung/*drug effects/metabolism/pathology, Middle Aged, Mustard Gas/*poisoning, Oxidative stress, Oxidative Stress/*drug effects, Reactive Oxygen Species, Reactive Oxygen Species/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Sulfur Mustard, Transcriptome/*drug effects, Young Adult
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.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/27085470
DOI10.1016/j.mrgentox.2016.03.006
Short TitleGene expression profile of oxidative stress and antioxidant defense in lung tissue of patients exposed to sulfur mustard

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