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Toxicology Letters Sep 2018Phosgene Oxime (CX, ClCNOH), a halogenated oxime, is a potent chemical weapon that causes immediate acute injury and systemic effects. CX, grouped together with... (Review)
Review
Phosgene Oxime (CX, ClCNOH), a halogenated oxime, is a potent chemical weapon that causes immediate acute injury and systemic effects. CX, grouped together with vesicating agents, is an urticant or nettle agent with highly volatile, reactive, corrosive, and irritating vapor, and has considerably different chemical properties and toxicity compared to other vesicants. CX is absorbed quickly through clothing with faster cutaneous penetration compared to other vesicating agents causing instantaneous and severe damage. For this reason, it could be produced as a weaponized mixture with other chemical warfare agents to enhance their deleterious effects. The immediate devastating effects of CX and easy synthesis makes it a dangerous chemical with both military and terrorist potentials. Although CX is the most potent vesicating agent, it is one of the least studied chemical warfare agents and the pathophysiology as well as long term effects are largely unknown. CX exposure results in immediate pain and inflammation, and it mainly affects skin, eye and respiratory system. There are no antidotes available against CX-induced injury and the treatment is only supportive. This review summarizes existing knowledge regarding exposure, toxicity and the probable underlying mechanisms of CX compared to other important vesicants' exposure.
Topics: Animals; Antidotes; Arsenic Poisoning; Arsenicals; Blister; Chemical Warfare Agents; Humans; Irritants; Mustard Gas; Phosgene; Poisoning; Skin Diseases
PubMed: 29141200
DOI: 10.1016/j.toxlet.2017.11.011 -
The Journal of General Physiology Nov 1948The action of mustard gas on six animal, one plant, and two bacterial viruses; also on bacteria, yeast, and the pneumococcus-transforming principle has been studied. The...
The action of mustard gas on six animal, one plant, and two bacterial viruses; also on bacteria, yeast, and the pneumococcus-transforming principle has been studied. The viruses include Newcastle's disease of chickens, equine encephalomyelitis (Eastern strain), feline pneumonitis (Baker), rabbit papilloma (Shope), fixed rabies, rabbit myxoma, tobacco mosaic, T(2)r(+) phage of E. coli B, and a Staphylococcus muscae phage. The cells include bakers' yeast, E. coli B, Staphylococcus muscae, and swine plague bacillus. The rates of inactivation of the viruses and cells were of the same order of magnitude and faster than those of enzymes. Of the viruses examined those containing desoxyribose nucleic acid were inactivated faster than those containing ribosenucleic acid. Preparations of the pneumococcus-transforming principle which were largely desoxyribose nucleic acid have shown the greatest sensitivity to mustard gas of all systems examined. An expression was derived describing the inactivation rate when mustard gas decreases during the experiment.
Topics: Animals; Bacillus; Bacteria; DDT; Escherichia coli; Mustard Gas; Saccharomyces cerevisiae; Swine; Viruses
PubMed: 18891148
DOI: 10.1085/jgp.32.2.221 -
Annals of the New York Academy of... Aug 2010Sulfur mustard (SM) is a chemical weapon that targets the skin, eyes, and lung. It was first employed during World War I and it remains a significant military and... (Review)
Review
Sulfur mustard (SM) is a chemical weapon that targets the skin, eyes, and lung. It was first employed during World War I and it remains a significant military and civilian threat. As a bifunctional alkylating agent, SM reacts with a variety of macromolecules in target tissues including nucleic acids, proteins and lipids, as well as small molecular weight metabolites such as glutathione. By alkylating subcellular components, SM disrupts metabolism, a process that can lead to oxidative stress. Evidence for oxidative stress in tissues exposed to SM or its analogs include increased formation of reactive oxygen species, the presence of lipid peroxidation products and oxidized proteins, and increases in antioxidant enzymes such as superoxide dismutase, catalase, and glutathione-S-transferase. Inhibition of antioxidant enzymes including thioredoxin reductase by SM can also disrupt cellular redox homeostasis. Consistent with these findings, SM-induced toxicity has been shown to be reduced by antioxidants in both in vitro and in vivo models. These data indicate that drugs that target oxidative stress pathways may represent important candidates for reducing SM-induced tissue injury.
Topics: Animals; Antioxidants; Humans; Lung Injury; Mustard Gas; Oxidants; Oxidative Stress
PubMed: 20716289
DOI: 10.1111/j.1749-6632.2010.05605.x -
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 -
Annals of the New York Academy of... Aug 2016In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the... (Review)
Review
In mouse skin, sulfur mustard (SM) is a potent vesicant, damaging both the epidermis and the dermis. The extent of wounding is dependent on the dose of SM and the duration of exposure. Initial responses include erythema, pruritus, edema, and xerosis; this is followed by an accumulation of inflammatory leukocytes in the tissue, activation of mast cells, and the release of mediators, including proinflammatory cytokines and bioactive lipids. These proinflammatory mediators contribute to damaging the epidermis, hair follicles, and sebaceous glands and to disruption of the epidermal basement membrane. This can lead to separation of the epidermis from the dermis, resulting in a blister, which ruptures, leading to the formation of an eschar. The eschar stimulates the formation of a neoepidermis and wound repair and may result in persistent epidermal hyperplasia. Epidermal damage and repair is associated with upregulation of enzymes generating proinflammatory and pro-growth/pro-wound healing mediators, including cyclooxygenase-2, which generates prostanoids, inducible nitric oxide synthase, which generates nitric oxide, fibroblast growth factor receptor 2, and galectin-3. Characterization of the mediators regulating structural changes in the skin during SM-induced tissue damage and wound healing will aid in the development of therapeutic modalities to mitigate toxicity and stimulate tissue repair processes.
Topics: Animals; DNA Damage; Inflammation Mediators; Mice; Mustard Gas; Skin; Skin Diseases; Wound Healing
PubMed: 27371823
DOI: 10.1111/nyas.13125 -
Chinese Journal of Traumatology =... 2013To review long-term respiratory effects of mustard gas on Iranian veterans having undergone Iraq-Iran war. Electronic databases of Scopus, Medline, ISI, IranMedex, and... (Review)
Review
To review long-term respiratory effects of mustard gas on Iranian veterans having undergone Iraq-Iran war. Electronic databases of Scopus, Medline, ISI, IranMedex, and Irandoc sites were searched. We accepted articles published in scientific journals as a quality criterion.The main pathogenic factors are free radical mediators. Prevalence of pulmonary involvement is approximately 42.5%. The most common complaints are cough and dyspnea. Major respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, and asthma. Spirometry results can reveal restrictive and obstructive pulmonary disease. Plain chest X-ray does not help in about 50% of lung diseases. High-resolution CT of the lung is the best modality for diagnostic assessment of parenchymal lung and bronchi. There is no definite curative treatment for mustard lung. The effective treatment regimens consist of oxygen administration, use of vaporized moist air, respiratory physiotherapy, administration of mucolytic agents, bronchodilators, corticosteroids, and long-acting beta-2 agonists, antioxidants, surfactant, magnesium ions, therapeutic bronchoscopy, laser therapy, placement of respiratory stents, early tracheostomy in laryngospasm, and ultimately lung transplantation. High-resolution CT of the lung is the most accurate modality for the evaluation of the lung parenchyma and bronchi. The treatment efficacy of patients exposed to mustard gas depends on patient conditions (acute or chronic, upper or lower respiratory tract involvement). There are various treatment protocols, but unfortunately none of them is definitely curable.
Topics: Adult; Chemical Warfare; Chemical Warfare Agents; Humans; Iran; Lung; Lung Injury; Male; Middle Aged; Mustard Gas; Respiratory System; Survivors; Tomography, X-Ray Computed; Veterans
PubMed: 23735551
DOI: No ID Found -
Current Opinion in Allergy and Clinical... Apr 2013New literature from 2009 to 2012 regarding occupational constrictive bronchiolitis challenges textbook descriptions of this disease, formerly thought to be limited to... (Review)
Review
PURPOSE OF REVIEW
New literature from 2009 to 2012 regarding occupational constrictive bronchiolitis challenges textbook descriptions of this disease, formerly thought to be limited to fixed airflow limitation arising in the wake of accidental overexposure to noxious chemicals. Indolent evolution of dyspnea without a recognized hazardous exposure is a more common presentation.
RECENT FINDINGS
Biopsy-confirmed case series of constrictive bronchiolitis from US soldiers, Iranian survivors of sulfur mustard gassing, hospital-based studies, and flavoring-related cases document that indolent constrictive bronchiolitis cases can have normal spirometry or either restrictive or obstructive abnormalities. High-resolution computerized tomography studies can be normal or reflect air-trapping and mosaic attenuation on expiratory films. Thus, in the absence of noninvasive abnormalities, the diagnosis in dyspneic patients may require thoracoscopic biopsy in settings in which exposure risk has not been recognized. Many workers with occupational constrictive bronchiolitis stabilize with cessation of exposures causing bronchiolar epithelial necrosis.
SUMMARY
Clinicians need a high index of suspicion for constrictive bronchiolitis in young patients with rapidly progressing exertional dyspnea, regardless of spirometric and radiologic findings. Identification of novel causes and exposure-response relations for known causes are needed to provide guidance for protecting workers at risk for this largely irreversible lung disease.
Topics: Bronchiolitis Obliterans; Chemical Warfare Agents; Humans; Iran; Military Personnel; Mustard Gas; Occupational Diseases; Occupational Exposure; Tomography, X-Ray Computed; United States; Young Adult
PubMed: 23407121
DOI: 10.1097/ACI.0b013e32835e0282 -
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 Ophthalmic & Vision Research 2017To develop clinical practice guidelines (CPGs) for prevention, diagnosis, treatment and follow-up of ocular injuries caused by exposure to mustard gas.
PURPOSE
To develop clinical practice guidelines (CPGs) for prevention, diagnosis, treatment and follow-up of ocular injuries caused by exposure to mustard gas.
METHODS
The clinical questions were designed by the guideline team. Websites and databases including National Guidelines Clearinghouse, National Institute for Clinical Excellence, Cochrane, and PubMed were searched to find related CPGs and explore possible answers to the clinical questions. Since there were no relevant CPGs in the literature, related articles in Persian and English languages were extracted. Each article along with its level of evidence was summarized. Additionally, hand search was performed by looking the reference list of each article. Consequently, recommendations were developed considering the clinical benefits and side effects of each therapeutic modality. The recommendations were re-evaluated in terms of customization criteria. All recommendations along with the related evidence were scored from 1 to 9 by experts from all medical universities of Iran. The level of agreement among the experts was evaluated by analyzing the given scores.
RESULTS
The agreement was achieved for all recommendations. The experts suggested a number of minor modifications which were applied to the recommendations. Finally, CPGs were developed with 98 recommendations under three major domains including prevention of injury, diagnosis and management of the acute and delayed-onset mustard gas ocular injuries.
CONCLUSION
Considering the lack of CPGs for the prevention, diagnosis, and management of mustard gas-induced keratitis, these recommendations would be useful to prevent the serious ocular complications of mustard gas and standardize eye care services to the affected individuals.
PubMed: 28299009
DOI: 10.4103/jovr.jovr_253_16 -
Toxicology and Applied Pharmacology Jan 2009The biochemical sequelae to chloroethyl mustard exposure correspond very well to toxic processes initiated by free radicals. Additionally, mustard solutions contain...
The biochemical sequelae to chloroethyl mustard exposure correspond very well to toxic processes initiated by free radicals. Additionally, mustard solutions contain spontaneously formed cyclic onium ions which produce carbon free radicals when reduced electrochemically. Therefore, we hypothesized that the onium ions of sulfur or nitrogen mustards might produce carbon free radicals upon being reduced enzymatically, and that these radicals might constitute a metabolic activation. We set out to document radical production using an in vitro metabolic system and electron paramagnetic resonance (EPR). Our system consisted of NADPH, one of several pyridine nucleotide-driven flavoprotein reductases, cytochrome c as a terminal electron acceptor, various sulfur or nitrogen mustards and the spin trap alpha-[4-pyridyl-1-oxide]-N-tert-butylnitrone in buffer. Reactions were started by adding the reductase to the other materials, vortexing and immediately transferring the mixture to a 10 mm EPR flat cell. Repeated scans on a Bruker ESP 300E EPR spectrometer produced a triplet of doublets with hyperfine splitting constants of a(N)=15.483 G and a(H)=2.512 G. The outcome supported our hypothesis that carbon-centered free radicals are produced when mustard-related onium ions are enzymatically reduced. The EPR results varied little with the chloroethyl compound used or with porcine or human cytochrome P450 reductase, the reductase domain of rat brain neuronal nitric oxide synthase or rat liver thioredoxin reductase. Our results offer new insight into the basis for mustard-induced vesication and the outcome of exposure to different mustards. The free radical model provides an explanation for similarities in the lesions arising from mustard exposure and energy-based lesions such as those from heat, ultraviolet and nuclear radiation as well as damage across tissue types such as skin, eyes or airway epithelium.
Topics: Animals; Brain; Chemical Warfare Agents; Cytochromes c; Electron Spin Resonance Spectroscopy; Free Radicals; Humans; Liver; Mustard Gas; NADP; NADPH-Ferrihemoprotein Reductase; Nitric Oxide Synthase; Nitrogen Mustard Compounds; Pyridines; Rats; Spin Trapping; Swine; Thioredoxin-Disulfide Reductase
PubMed: 18977373
DOI: 10.1016/j.taap.2008.10.002