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Sulfur mustard induces expression of metallothionein-1A in human airway epithelial cells.

ABSTRACT: BACKGROUND:Sulfur mustard can cause several long-term complications in the organs of individuals exposed to this toxic gas, and among these, pulmonary sequelae are the most important. More than 25 years after the Iran-Iraq war, thousands of Iranians are suffering from the chronic respiratory complications of sulfur mustard. Currently, based on several clinical findings, bronchiolitis obliterans is confirmed as the major diagnosis in these patients. Numerous studies have revealed that this disorder is strongly associated with oxidative stress due to excessive production of harmful reactive substances and decreased levels of endogenous antioxidants. Metallothioneins (MTs) are a group of low molecular weight sulfhydryl-rich intra-cellular proteins, and several isoforms have been identified in humans. MT-1A is an inducible and important MT isoform, which is transcriptionally activated by a variety of stress stimuli, such as free radicals. METHODS:MT-1 mRNA expression and protein levels in endobronchial biopsy samples from 24 sulfur mustard-exposed patients and 15 unexposed control cases were evaluated by semi-quantitative reverse transcriptase polymerase chain reaction, real-time reverse transcriptase polymerase chain reaction, and immunohistochemistry. RESULTS:mRNA- MT-1A expression levels in sulfur mustard-exposed patients were upregulated compared with normal samples. Protein expression was also markedly higher in controls than in sulfur mustard-exposed patients. CONCLUSION:Upregulation of MT-1A mRNA in patients who have been exposed to sulfur mustard seems to be due to oxidative stress, which is induced in an attempt to ameliorate this harmful situation by reestablishment of homeostasis, but depletion of its protein might be due to secondary consequences of sulfur mustard toxicity, which are as yet not understood.

SUBMITTER: Nourani MR

PROVIDER: S-EPMC3119583 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Sulfur mustard induces expression of metallothionein-1A in human airway epithelial cells.

Nourani Mohammad Reza MR Ebrahimi Majid M Roudkenar Mehryar Habibi MH Vahedi Ensieh E Ghanei Mostafa M Imani Fooladi Abbas Ali AA

International journal of general medicine 20110526

<h4>Background</h4>Sulfur mustard can cause several long-term complications in the organs of individuals exposed to this toxic gas, and among these, pulmonary sequelae are the most important. More than 25 years after the Iran-Iraq war, thousands of Iranians are suffering from the chronic respiratory complications of sulfur mustard. Currently, based on several clinical findings, bronchiolitis obliterans is confirmed as the major diagnosis in these patients. Numerous studies have revealed that thi ...[more]

PMID: 21731892

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Project description:Sulfur mustard (SM) is a chemical weapon stockpiled today in volatile regions of the world. SM inhalation causes a life-threatening airway injury characterized by airway obstruction from fibrin casts, which can lead to respiratory failure and death. Mortality in those requiring intubation is more than 80%. No therapy exists to prevent mortality after SM exposure. Our previous work using the less toxic analog of SM, 2-chloroethyl ethyl sulfide, identified tissue plasminogen activator (tPA) an effective rescue therapy for airway cast obstruction (Veress, L. A., Hendry-Hofer, T. B., Loader, J. E., Rioux, J. S., Garlick, R. B., and White, C. W. (2013). Tissue plasminogen activator prevents mortality from sulfur mustard analog-induced airway obstruction. Am. J. Respir. Cell Mol. Biol. 48, 439-447). It is not known if exposure to neat SM vapor, the primary agent used in chemical warfare, will also cause death due to airway casts, and if tPA could be used to improve outcome.Adult rats were exposed to SM, and when oxygen saturation reached less than 85% (median: 6.5?h), intratracheal tPA or placebo was given under isoflurane anesthesia every 4?h for 48?h. Oxygen saturation, clinical distress, and arterial blood gases were assessed. Microdissection was done to assess airway obstruction by casts.Intratracheal tPA treatment eliminated mortality (0% at 48?h) and greatly improved morbidity after lethal SM inhalation (100% death in controls). tPA normalized SM-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress. Moreover, tPA treatment resulted in greatly diminished airway casts, preventing respiratory failure from airway obstruction.tPA given via airway more than 6?h after exposure prevented death from lethal SM inhalation, and normalized oxygenation and ventilation defects, thereby rescuing from respiratory distress and failure. Intra-airway tPA should be considered as a life-saving rescue therapy after a significant SM inhalation exposure incident.

Dataset Information

Sulfur mustard induces expression of metallothionein-1A in human airway epithelial cells.

Publications

Sulfur mustard induces expression of metallothionein-1A in human airway epithelial cells.

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