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Journal of Cellular and Molecular... Aug 2023Sulfur mustard (SM) is a blister-producing chemical warfare agent which could lead to a cascade of systemic damage, especially severe acute lung injury. Oxidative stress...
Sulfur mustard (SM) is a blister-producing chemical warfare agent which could lead to a cascade of systemic damage, especially severe acute lung injury. Oxidative stress is considered to be vital processes for the SM toxicity mechanism. We previously proved the therapeutic effect of exosomes derived from bone marrow mesenchymal stromal cells in promoting the repair of alveolar epithelial barrier and inhibiting apoptosis. However, the key functional components in exosomes and the underlying mechanisms have not been fully elaborated. This research shed light on the function of the key components of human umbilical cord mesenchymal stem cell-derived exosomes (HMSCs-Ex). We noted that HMSCs-Ex-derived miR-199a-5p played a vital role in reducing pneumonocyte oxidative stress and apoptosis by reducing reactive oxygen species, lipid peroxidation products and increasing the activities of antioxidant enzymes in BEAS-2B cells and mouse models after exposure to SM for 24 h. Furthermore, we demonstrated that the overexpression of miR-199a-5p in HMSCs-Ex treatment induced a further decrease of Caveolin1 and the activation of the mRNA and protein level of NRF2, HO1 and NQO1, compared with HMSCs-Ex administration. In summary, miR-199a-5p was one of the key molecules in HMSCs-Ex that attenuated SM-associated oxidative stress via regulating CAV1/NRF2 signalling pathway.
Topics: Animals; Humans; Mice; Exosomes; Mesenchymal Stem Cells; MicroRNAs; Mustard Gas; NF-E2-Related Factor 2; Oxidative Stress
PubMed: 37386746
DOI: 10.1111/jcmm.17803 -
Lung Aug 2021The case definition of inhalational constrictive bronchiolitis (CB) has changed over the generations. We identify changes in the description of this illness over time... (Review)
Review
The case definition of inhalational constrictive bronchiolitis (CB) has changed over the generations. We identify changes in the description of this illness over time associated with different exposures and present the natural history of CB in a case attributed to military burn pit exposure. The initial descriptions of this disease began with nitric acid spills and silage exposures. In these events, there was an acute exposure, typically a short-term resolution of the adverse respiratory events, and then a progression, leading to disability or a respiratory death. The life-saving role of corticosteroid therapy in this situation was recognized. War gas exposures of World War I and then Saddam Hussein's use of sulfur mustard gas in the Iran-Iraq War followed. More recently the findings associated with diacetyl exposure in commercial popcorn workers remained consistent with previously described presentations, but then the clinical presentation in troops returning from deployment to Southwest Asia was very different, yet with the same histologic findings. We recognize unreconciled disparities in the clinical, physiologic, and imaging presentation in those with inhalational bronchiolitis and acknowledge this as perhaps one of the difficult diagnoses in respiratory medicine.
Topics: Biopsy; Bronchiolitis Obliterans; Humans; Middle East; Military Personnel; Tomography, X-Ray Computed
PubMed: 34415399
DOI: 10.1007/s00408-021-00466-2 -
Antibiotics (Basel, Switzerland) Feb 2023Organic selenocyanates (RSeCN) are among the most reactive and biologically active Se species, often exhibiting a pronounced cytotoxic activity against mammalian cells...
Organic selenocyanates (RSeCN) are among the most reactive and biologically active Se species, often exhibiting a pronounced cytotoxic activity against mammalian cells and microorganisms. Various aromatic selenocyanates have been synthesized and, similar to some of the most Reactive Sulfur Species (RSS), such as allicin, found to be active against a range of bacteria, including , and , and fungi, including , , , and , even via the gas phase. The highest antimicrobial activity has been observed for benzyl selenocyanate, which inhibited the growth of all bacteria considerably, even at the lowest tested concentration of 50 µM. Notably, neither the analogues thiocyanate (BTC) nor isothiocyanate (BITC) show any of these activities, rendering this selenium motif rather special in activity and mode of action. Eventually, these findings advocate a range of potential applications of organic selenocyanates in medicine and agriculture.
PubMed: 36830201
DOI: 10.3390/antibiotics12020290 -
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 -
Toxicology Nov 2021Blister agents damage the skin, eyes, mucous membranes and subcutaneous tissues. Other toxic effects may occur after absorption. The response of the Scientific Advisory... (Review)
Review
Advice on assistance and protection provided by the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons: Part 3. On medical care and treatment of injuries from sulfur mustard.
Blister agents damage the skin, eyes, mucous membranes and subcutaneous tissues. Other toxic effects may occur after absorption. The response of the Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) to a request from the OPCW Director-General in 2013 on the status of medical countermeasures and treatments to blister agents is updated through the incorporation of the latest information. The physical and toxicological properties of sulfur mustard and clinical effects and treatments are summarised. The information should assist medics and emergency responders who may be unfamiliar with the toxidrome of sulfur mustard and its treatment.
Topics: Animals; Chemical Warfare Agents; Humans; Medical Countermeasures; Mustard Gas
PubMed: 34619302
DOI: 10.1016/j.tox.2021.152967 -
The Journal of Pharmacology and... Jan 2024The chemical warfare agent sulfur mustard and its structural analog nitrogen mustard (NM) cause severe vesicating skin injuries. The pathologic mechanisms for the skin...
The chemical warfare agent sulfur mustard and its structural analog nitrogen mustard (NM) cause severe vesicating skin injuries. The pathologic mechanisms for the skin injury following mustard exposure are poorly understood; therefore, no effective countermeasure is available. Previous reports demonstrated the protective activity of carvedilol, a US Food and Drug Administration (FDA)-approved -blocker, against UV radiation-induced skin damage. Thus, the current study evaluated the effects of carvedilol on NM-induced skin injuries in vitro and in vivo. In the murine epidermal cell line JB6 Cl 41-5a, -blockers with different receptor subtype selectivity were examined. Carvedilol and both of its enantiomers, R- and S-carvedilol, were the only tested ligands statistically reducing NM-induced cytotoxicity. Carvedilol also reduced NM-induced apoptosis and p53 expression. In SKH-1 mice, NM increased epidermal thickness, damaged skin architecture, and induced nuclear factor B (NF-B)-related proinflammatory genes as assessed by RT Profiler PCR (polymerase chain reaction) Arrays. To model chemical warfare scenario, 30 minutes after exposure to NM, 10 M carvedilol was applied topically. Twenty-four hours after NM exposure, carvedilol attenuated NM-induced epidermal thickening, Ki-67 expression, a marker of cellular proliferation, and multiple proinflammatory genes. Supporting the in vitro data, the non--blocking R-enantiomer of carvedilol had similar effects as racemic carvedilol, and there was no difference between carvedilol and R-carvedilol in the PCR array data, suggesting that the skin protective effects are independent of the -adrenergic receptors. These data suggest that the -blocker carvedilol and its enantiomers can be repurposed as countermeasures against mustard-induced skin injuries. SIGNIFICANCE STATEMENT: The chemical warfare agent sulfur mustard and its structural analog nitrogen mustard cause severe vesicating skin injuries for which no effective countermeasure is available. This study evaluated the effects of US Food and Drug Administration (FDA)-approved -blocker carvedilol on nitrogen mustard-induced skin injuries to repurpose this cardiovascular drug as a medical countermeasure.
Topics: Animals; Mice; Mechlorethamine; Carvedilol; Chemical Warfare Agents; Mustard Gas; Skin; Adrenergic beta-Antagonists
PubMed: 37827703
DOI: 10.1124/jpet.123.001663 -
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 -
Ecotoxicology and Environmental Safety Dec 2021As a natural heme protein catalyzing the oxidation of sulfides to sulfoxides without sulfone formation, chloroperoxidase (CPO) is well suited for the degradation of...
As a natural heme protein catalyzing the oxidation of sulfides to sulfoxides without sulfone formation, chloroperoxidase (CPO) is well suited for the degradation of sulfur mustard (HD), a persistent chemical warfare agent that has been widely disposed since World War II and continuously leaks into aquatic environments. Herein, we report the first systematic investigation of CPO-catalyzed degradation of HD and the potential application of CPO in destroying chemical weapons under mild conditions. The related Michaelis-Menten parameters (K=0.17 mM, V=0.06 mM s (R =0.935), and k= 2717 s) indicated nearly a prominent enzymatic efficiency. Under optimal conditions, 80% of HD was transformed to bis(2-chloroethyl) sulfoxide as identified by mass spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. Other metabolites were also generated during the decontamination process. A plausible oxidation mechanism was proposed based on the degradation products, NMR titration experiments, and molecular dynamics simulations. CPO also promoted the degradation of other chemical weapon agents, namely, Lewisite (L) and venomous agent X (VX), thereby exhibiting a broad substrate scope. The high potential of the developed system for the decontamination of aquatic environments was demonstrated by the successful hatching of zebrafish embryos after HD degradation and the survival of zebrafish (Danio rerio, AB strain) larvae after the degradation of Agent Yellow (L+HD).
Topics: Animals; Catalysis; Chloride Peroxidase; Mustard Gas; Oxidative Stress; Zebrafish
PubMed: 34500382
DOI: 10.1016/j.ecoenv.2021.112715 -
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 -
Seminars in Ophthalmology May 2021The investigations discussed in this review indicate that iron may exacerbate different eye diseases. Therefore, it is plausible that reducing cellular or body iron... (Review)
Review
The investigations discussed in this review indicate that iron may exacerbate different eye diseases. Therefore, it is plausible that reducing cellular or body iron stores could influence disease pathogenesis, so it is logical to consider the iron chelators' potential protective role in the various ophthalmic diseases in the form of topical eye drops or slow releasing injectable compounds as an adjuvant treatment.
Topics: Eye Diseases; Humans; Iron; Iron Chelating Agents; Macular Degeneration; Ophthalmic Solutions
PubMed: 33621147
DOI: 10.1080/08820538.2021.1887900