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Interdisciplinary Toxicology Nov 2017Sulphur mustard (SM) is a powerful blister-causing alkylating chemical warfare agent used by Iraqi forces against Iran. One of the known complications of mustard gas... (Review)
Review
Sulphur mustard (SM) is a powerful blister-causing alkylating chemical warfare agent used by Iraqi forces against Iran. One of the known complications of mustard gas inhalation is mustard lung which is discussed as a phenotype of chronic obstructive pulmonary disease (COPD). In this complication, there are clinical symptoms close to COPD with common etiologies, such as in smokers. Based on information gradually obtained by conducting the studies on mustard lung patients, systemic symptoms along with pulmonary disorders have attracted the attention of researchers. Changes in serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), nuclear factor κB (NF-κB), matrix metalloproteinases (MMPs), interleukin (IL), chemokines, selectins, immunoglobulins, and signs of imbalance in oxidant-antioxidant system at serum level, present the systemic changes in these patients. In addition to these, reports of extra-pulmonary complications, such as osteoporosis and cardiovascular disease are also presented. In this study, the chance of developing the systemic nature of this lung disease have been followed on using the comparative study of changes in the mentioned markers in mustard lung and COPD patients at stable phases and the mechanisms of pathogenesis and phenomena, such as airway remodeling in these patients.
PubMed: 30174535
DOI: 10.1515/intox-2017-0018 -
Annals of the New York Academy of... Jun 2016Sulfur mustard (SM) and nitrogen mustard (NM) are cytotoxic alkylating agents that cause severe and progressive injury to the respiratory tract, resulting in significant... (Review)
Review
Sulfur mustard (SM) and nitrogen mustard (NM) are cytotoxic alkylating agents that cause severe and progressive injury to the respiratory tract, resulting in significant morbidity and mortality. Evidence suggests that macrophages and the inflammatory mediators they release play roles in both acute and long-term pulmonary injuries caused by mustards. In this article, we review the pathogenic effects of SM and NM on the respiratory tract and potential inflammatory mechanisms contributing to this activity.
Topics: Animals; Humans; Inflammation Mediators; Irritants; Lung; Lung Injury; Macrophages; Mustard Gas
PubMed: 27351588
DOI: 10.1111/nyas.13123 -
BMC Pulmonary Medicine Dec 2022Respiratory diseases are the leading cause of morbidity and mortality in the survivors exposed to Sulfur Mustard (SM). The late abnormalities can be present as chronic...
BACKGROUND
Respiratory diseases are the leading cause of morbidity and mortality in the survivors exposed to Sulfur Mustard (SM). The late abnormalities can be present as chronic bronchitis, tracheobronchial stenosis, asthma, bronchiectasis, airway narrowing, lung fibrosis, and lung cancers. This study aims to investigate the association between radiological findings and lung cancer development in patients exposed to sulfur mustard gas.
METHODS
We entered 719 victims exposed to SM during the Iran-Iraq war into our follow-up study in a consensus manner. They were periodically followed with Chest HRCT scans from 2001 to an interval of 2014-2019. The mean year interval between exposure and the last follow-up was 38 years. For confirming the lung cancer in those with evidence of malignancy in their imaging, fine needle aspiration/biopsy and/or surgical intervention were done.
RESULTS
Among 719 patients, 57% were free from any pathologic findings in their HRCT scan. Among the subjects who had the abnormal radiologic findings, Air Trapping (AT), Lung Fibrosis (LF), Bronchiectasis (B), and the evidence of lung cancer were found in 265 (36.9%), 207 (28.8%), 151 (21.0%), and 42 (5.8%), respectively. Adenocarcinoma (38.1%) was the most common type of cancer. The right lung was involved more than the left one regarding LF, B, and cancer (p value < 0.05). Considering the laterality, a significant correlation was found between the side of LF and B and the tumor side. Furthermore, it was shown that the lung lobes with LF were statistically correlated to tumor-involved lobes. The relative risk of AT and B existence for tumor development was 11.73 [4.87-28.26] and 10.14 [5.12-20.090], respectively. The most predictive finding was LF which caused the risk of developing tumor 17.75 [7.35-42.86] times higher in the patient with this pathology. By each increment of the number of LF and B, the risk of developing tumors increased by 51% and 76%, respectively.
CONCLUSION
In survivors exposed to Sulfur Mustard, those with bronchiectasis and lung fibrosis have a significantly higher risk of developing lung cancers, so a close follow-up of these victims is recommended. Trial registration This study was confirmed by the institutional review board and ethics committee at Shiraz University of Medical Sciences (SUMS) with the ethical code IR.SUMS.MED.REC.1399.637.
Topics: Humans; Mustard Gas; Follow-Up Studies; Pulmonary Fibrosis; Chemical Warfare Agents; Lung Neoplasms; Bronchiectasis; Respiration Disorders; Iran
PubMed: 36539770
DOI: 10.1186/s12890-022-02282-7 -
RSC Advances Sep 2023Methyl-diethanolamine (CAS: 105-59-9), ethyl-diethanolamine (CAS: 139-87-7), and triethanolamine (CAS: 102-71-6) were identified as the degradation products and...
Fluoride derivatization-enabled sensitive and simultaneous detection of biomarkers for nitrogen mustard in human plasma and urine gas chromatography tandem mass spectrometry.
Methyl-diethanolamine (CAS: 105-59-9), ethyl-diethanolamine (CAS: 139-87-7), and triethanolamine (CAS: 102-71-6) were identified as the degradation products and bio-markers of nitrogen mustard exposure. Sensitive and convenient detection methods for amino alcohol are of great importance to identify nitrogen mustard exposure in forensic analysis. Herein, analytical methods including gas chromatography-tandem mass spectrometry combined with heptafluorobutyryl derivatization and solid phase extraction were established for retrospective detection of the biomarkers in human plasma and urine samples. The efficiency of the method was improved by optimizing the conditions for sample preparation and the GC-MS/MS method. The optimization included the derivatization temperature, reaction time, reagent dosage and solid phase extraction cartridges, eluent and pH of the loading sample. The results indicated that the SCX cartridge resulted in better enrichment and purification effects, and the best recovery could be obtained with pH = 3-4 for the loading samples and an eluent of 2 mL 10% NHOH/MeOH. The GC-MS/MS parameters were also optimized for better specificity and sensitivity. The established method was fully validated for each analyte both in plasma and urine matrixes. The linear range of analytes in plasma was 1.0-1000 ng mL with a correlation parameter () of ≥0.994, intra-day/inter-day accuracy of 93.7-117%, and relative standard deviation (RSD) of ≤6.5%. Meanwhile the results in urine were 1.0-1000 ng mL with of ≥0.996, intra-day/inter-day accuracy of 94.3-122%, and RSD of ≤6.6%. The detection limit of the analytes was 1.0 ng mL. The method was applied for the detection and identification of trace amino alcohols present in urine samples dispatched by the Organization for the Prohibition of Chemical Weapons (OPCW) and the results were confirmed to be correct.
PubMed: 37720833
DOI: 10.1039/d3ra04697d -
Experimental Eye Research May 2023Sulfur mustard (SM) is a chemical warfare agent (CWA) that causes severe eye pain, photophobia, excessive lacrimation, corneal and ocular surface defects, and blindness....
Sulfur mustard (SM) is a chemical warfare agent (CWA) that causes severe eye pain, photophobia, excessive lacrimation, corneal and ocular surface defects, and blindness. However, SM's effects on retinal cells are relatively meager. This study investigated the role of SM toxicity on Müller glial cells responsible for cellular architecture, inner blood-retinal barrier maintenance, neurotransmitter recycling, neuronal survival, and retinal homeostasis. Müller glial cells (MIO-M1) were exposed to SM analog, nitrogen mustard (NM), at varying concentrations (50-500 μM) for 3 h, 24 h, and 72 h. Müller cell gliosis was evaluated using morphological, cellular, and biochemical methods. Real-time cellular integrity and morphological evaluation were performed using the xCELLigence real-time monitoring system. Cellular viability and toxicity were measured using TUNEL and PrestoBlue assays. Müller glia hyperactivity was calculated based on glial fibrillary acidic protein (GFAP) and vimentin immunostaining. Intracellular oxidative stress was measured using DCFDA and DHE cell-based assays. Inflammatory markers and antioxidant enzyme levels were determined by quantitative real-time PCR (qRT-PCR). AO/Br and DAPI staining further evaluated DNA damage, apoptosis, necrosis, and cell death. Inflammasome-associated Caspase-1, ASC, and NLRP3 were studied to identify mechanistic insights into NM toxicity in Müller glial cells. The cellular and morphological evaluation revealed the Müller glia hyperactivity after NM exposure in a dose- and time-dependent manner. NM exposure caused significant oxidative stress and enhanced cell death at 72 h. A significant increase in antioxidant indices was observed at the lower concentrations of NM. Mechanistically, we found that NM-treated MIO-M1 cells increased caspase-1 levels that activated NLRP3 inflammasome-induced production of IL-1β and IL-18, and elevated Gasdermin D (GSDMD) expression, a crucial component actuating pyroptosis. In conclusion, NM-induced Müller cell gliosis via increased oxidative stress results in caspase-1-dependent activation of the NLRP3 inflammasome and cell death driven primarily by pyroptosis.
Topics: Humans; Ependymoglial Cells; Gliosis; Mustard Gas; Antioxidants; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Caspases
PubMed: 37023936
DOI: 10.1016/j.exer.2023.109461 -
Immunity, Inflammation and Disease Nov 2023Respiratory disease (RD) is one of the most common diseases characterized by lung dysfunction. Many diagnostic mechanisms have been used to identify the pathogenic... (Review)
Review
AIM
Respiratory disease (RD) is one of the most common diseases characterized by lung dysfunction. Many diagnostic mechanisms have been used to identify the pathogenic agents of responsible for RD. Among these, proteomics emerges as a valuable diagnostic method for pinpointing the specific proteins involved in RD pathogenesis. Therefore, in this study, for the first time, we examined the protein markers involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, bronchiolitis obliterans (BO), and chemical warfare victims exposed to mustard gas, using the proteomics method as a systematic study.
MATERIALS AND METHODS
A systematic search was performed up to September 2023 on several databases, including PubMed, Scopus, ISI Web of Science, and Cochrane. In total, selected 4246 articles were for evaluation according to the criteria. Finally, 119 studies were selected for this systematic review.
RESULTS
A total of 13,806 proteins were identified, 6471 in COPD, 1603 in Asthma, 5638 in IPF, three in BO, and 91 in mustard gas exposed victims. Alterations in the expression of these proteins were observed in the respective diseases. After evaluation, the results showed that 31 proteins were found to be shared among all five diseases.
CONCLUSION
Although these 31 proteins regulate different factors and molecular pathways in all five diseases, they ultimately lead to the regulation of inflammatory pathways. In other words, the expression of some proteins in COPD and mustard-exposed patients increases inflammatory reactions, while in IPF, they cause lung fibrosis. Asthma, causes allergic reactions due to T-cell differentiation toward Th2.
Topics: Humans; Lung; Mustard Gas; Proteomics; Pulmonary Disease, Chronic Obstructive; Asthma; Biomarkers
PubMed: 38018577
DOI: 10.1002/iid3.1090 -
Journal of Chromatography. A Jan 2021Commercial gas chromatograph-mass spectrometers, one of which being Inficon's HAPSITE® ER, have demonstrated chemical detection and identification of nerve agents...
Commercial gas chromatograph-mass spectrometers, one of which being Inficon's HAPSITE® ER, have demonstrated chemical detection and identification of nerve agents (G-series) and blistering agents (mustard gas) in the field; however most analyses relies on self-contained or external calibration that inherently drifts over time. We describe an analytical approach that uses target-based thermal desorption standards, called focusing agents, to accurately calculate concentrations of chemical warfare agents that are analyzed by gas chromatograph-mass spectrometry. Here, we provide relative response factors of focusing agents (2-chloroethyl ethyl sulfide, diisopropyl fluorophosphate, diethyl methylphosphonate, diethyl malonate, methyl salicylate, and dichlorvos) that are used to quantify concentrations of tabun, sarin, soman, cyclosarin and sulfur mustard loaded on thermal desorption tubes (Tenax® TA). Aging effects of focusing agents are evaluated by monitoring deviations in quantification as thermal desorption tubes age in storage at room temperature and relative humidity. The addition of focusing agents improves the quantification of tabun, sarin, soman, cyclosarin and sulfur mustard that is analyzed within the same day as well as a 14-day period. Among the six focusing agents studied here, diisopropyl fluorophosphate has the best performance for nerve agents (G-series) and blistering agents (mustard gas) compared to other focusing agents in this work and is recommended for field use for quantification. The use of focusing agent in the field leads to more accurate and reliable quantification of Tabun (GA), Sarin (GB), Soman (GD), Cyclosarin (GF) and Sulfur Mustard (HD) than the traditional internal standard. Future improvements on the detection of chemical, biological, radiological, nuclear, and explosive materials (CBRNE) can be safely demonstrated with standards calibrated for harmful agents.
Topics: Chemical Warfare Agents; Gas Chromatography-Mass Spectrometry; Mustard Gas; Organophosphates; Organophosphorus Compounds; Reference Standards; Sarin; Soman
PubMed: 33360649
DOI: 10.1016/j.chroma.2020.461784 -
Genetics Feb 2017The numerous processes that damage DNA are counterbalanced by a complex network of repair pathways that, collectively, can mend diverse types of damage. Insights into... (Review)
Review
The numerous processes that damage DNA are counterbalanced by a complex network of repair pathways that, collectively, can mend diverse types of damage. Insights into these pathways have come from studies in many different organisms, including Drosophila melanogaster Indeed, the first ideas about chromosome and gene repair grew out of Drosophila research on the properties of mutations produced by ionizing radiation and mustard gas. Numerous methods have been developed to take advantage of Drosophila genetic tools to elucidate repair processes in whole animals, organs, tissues, and cells. These studies have led to the discovery of key DNA repair pathways, including synthesis-dependent strand annealing, and DNA polymerase theta-mediated end joining. Drosophila appear to utilize other major repair pathways as well, such as base excision repair, nucleotide excision repair, mismatch repair, and interstrand crosslink repair. In a surprising number of cases, however, DNA repair genes whose products play important roles in these pathways in other organisms are missing from the Drosophila genome, raising interesting questions for continued investigations.
Topics: Animals; DNA Repair; DNA Repair Enzymes; Drosophila; Drosophila Proteins; Models, Genetic; Mutagenesis
PubMed: 28154196
DOI: 10.1534/genetics.116.186759 -
Iranian Journal of Allergy, Asthma, and... Sep 2006Sulfur mustard has been employed in chemical warfare in certain regions including Iran. The short and long term biological effects of sulfur mustard contamination have... (Review)
Review
Sulfur mustard has been employed in chemical warfare in certain regions including Iran. The short and long term biological effects of sulfur mustard contamination have been studied in both basic and clinical aspects. Sulfur mustard has been shown to induce a vast array of pathological effects in affected persons. In addition to skin, lung, eyes and gastrointestinal disturbances, sulfur mustard has been shown to induce hematological complications and a severe suppression of the immune system. The short and long term immunological (both cellular and humoral), hematological, genetic and biochemical consequences of persons exposed to sulfur mustard are extensively reviewed here. The long term complications of these patients indicate the need to develop effective preventive and therapeutic strategies in the clinic. These strategies may be based upon immunopotentiating intervention and therapy.
Topics: Antibodies; Chemical Warfare Agents; Chromosome Aberrations; Humans; Immunosuppressive Agents; Leukopenia; Mustard Gas
PubMed: 17237560
DOI: No ID Found