Downregulation of super oxide dismutase level in protein might be due to sulfur mustard induced toxicity in lung.

Sulfur mustard (SM) has been identified as an important chemical weapon. During the Iran-Iraq war of 1980-88, the extensive usage of SM against Iranian civilians and military forces was proven. This agent has been shown to cause severe damage mainly in the skin, eyes, lungs, and respiratory tract in Iranian veterans. The most common disease is bronchiolitis obliterans (BO)). SM increases the endogenous production of reactive oxygen species (ROS). Superoxide dismutases (SODs) are known as protective antioxidants against the harmful effects of ROS. Twenty exposed SM individuals (43.2±6.4 years), and 10 normal controls (41.3±2.5 years) were enrolled in this study. Evaluation of SODs was performed by semiquantitative RT-PCR and immunohistochemistry. Our results demonstrated that CuZnSOD and MnSOD mRNA were up-regulated 2.79±1.09 and 2.49±1.11 folds, respectively in SM-injured patients in comparison with control levels. In contrast, Immunohistochemistry results showed downregulation of CuZnSOD protein expression in SM injured patients. Our results revealed that SODs may play an important role in cellular protection against oxidative stress due to mustard gas toxicity in airway wall of SM exposed patients.

Nuclear factor κB1/RelA mediates the inflammation and/or survival of human airway exposed to sulfur mustard.

CONTEXT: Sulfur mustard (SM) is known as an effective chemical agent and was used in the 1980s during the Iran-Iraq war against Iranians. At the present time, there are more than 40,000 people suffering from pulmonary lesions due to mustard gas in Iran. Though much is known about the gross pathology of SM damage, the molecular and cellular basis for this pathology is not well understood. OBJECTIVE: One of the most important protein groups involved in inflammatory responses is nuclear factor κB protein (NF-κB1) family. They belong to the category of DNA-binding protein factors necessary for transcription of many proinflammatory molecules. In our research, we examined the role of NF-κB1/RelA in the pathophysiology of the lung. MATERIALS AND METHODS: We investigated 10 normal individuals and 20 SM induced patients. Expression of NF-κB1/RelA in controls and the SM exposed samples was measured by real-time polymerase chain reaction and localization of NF-κB1 protein was detected by immunohistochemistry staining. RESULTS: Our results revealed that expression levels of NF-κB1 and RelA were upregulated 0.64-6.50 fold and 0.83-8.34 fold, respectively, in the SM exposed patients in comparison with control samples. DISCUSSION AND CONCLUSION: As far as we know, this is the first finding of induction of NF-κB in patients exposed to SM. NF-κB1/RelA may play a major role in inflammation induced by mustard gas or even in cell survival in the bronchial wall of affected patients.

HO1 mRNA and Protein do not Change in Parallel in Bronchial Biopsies of Patients After Long Term Exposure to Sulfur Mustard.

Sulfur mustard (SM), is an alkylating agent and has been emerged as a chemical weapon in various battlefields. More recently, SM was employed in the Iraq conflict against Iranian military forces and civilians. Nowadays there are more than 40,000 people suffering from pulmonary lesions special chronic obstructive pulmonary disease (COPD) due to mustard gas in Iran. SM causes the endogenous production of reactive oxygen species (ROS).Heme oxygenases (HOs) are the rate-limiting enzyme for heme metabolism. Numerous studies have confirmed that HOs are concerned in diverse biological processes such as anti-oxidation.The present study was undertaken to consider the regulation of HO-1 and HO-2 n the human airway wall, and to suggest a probable role that HOs may play in cellular defense against oxidative stress due to SM.In this research ten unexposed SM individuals and twenty SM exposed patients were included. Evaluation of HO-1& HO -2 expressions in unexposed and SM exposed patients samples was performed by semiquantitative RT-PCR, real-time RT-PCR and Immunohistochemistry analysis.While unexposed SM samples expressed same levels of HOs, expression level of HO-1 was upregulated about 3.58 ± 1.93 folds in SM exposed patients in comparison with unexposed ones, we could not find any difference in expression of HO-2 n two groups. In contrast, Immunohistochemistry results showed negative HO-1 protein expression in SM injured patients.Our results revealed that HO1 may plays an important role in cellular protection against oxidative stress due to mustard gas toxicity in airway wall of SM exposed patients at mRNA level, but translational modifications might cause decrease in the amount of HO1 protein.