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Toxicology Letters Feb 2020Sulfur mustard and related vesicants are cytotoxic alkylating agents that cause severe damage to the respiratory tract. Injury is progressive leading, over time, to... (Review)
Review
Sulfur mustard and related vesicants are cytotoxic alkylating agents that cause severe damage to the respiratory tract. Injury is progressive leading, over time, to asthma, bronchitis, bronchiectasis, airway stenosis, and pulmonary fibrosis. As there are no specific therapeutics available for victims of mustard gas poisoning, current clinical treatments mostly provide only symptomatic relief. In this article, the long-term effects of mustards on the respiratory tract are described in humans and experimental animal models in an effort to define cellular and molecular mechanisms contributing to lung injury and disease pathogenesis. A better understanding of mechanisms underlying pulmonary toxicity induced by mustards may help in identifying potential targets for the development of effective clinical therapeutics aimed at mitigating their adverse effects.
Topics: Alkylating Agents; Animals; Chemical Warfare Agents; Humans; Lung; Lung Injury; Mustard Compounds; Pulmonary Fibrosis; Respiratory Tract Diseases
PubMed: 31698045
DOI: 10.1016/j.toxlet.2019.10.026 -
International Journal of Molecular... Jun 2023Sulfur mustard (SM) is a highly toxic chemical agent that causes severe tissue damage, particularly to the eyes, lungs, and skin. Despite advances in treatment, there is... (Review)
Review
Sulfur mustard (SM) is a highly toxic chemical agent that causes severe tissue damage, particularly to the eyes, lungs, and skin. Despite advances in treatment, there is a need for more effective therapies for SM-induced tissue injury. Stem cell and exosome therapies are emerging as promising approaches for tissue repair and regeneration. Stem cells can differentiate into multiple cell types and promote tissue regeneration, while exosomes are small vesicles that can deliver therapeutic cargo to target cells. Several preclinical studies demonstrated the potential of stem cell, exosome, or combination therapy for various tissue injury, showing improvements in tissue repairing, inflammation, and fibrosis. However, there are also challenges associated with these therapies, such as the requirement for standardized methods for exosome isolation and characterization, the long-term safety and efficacy and reduced SM-induced tissue injury of these therapies. Stem cell or exosome therapy was used for SM-induced eye and lung injury. Despite the limited data on the use for SM-induced skin injury, this therapy is a promising area of research and may offer new treatment options in the future. In this review, we focused on optimizing these therapies, evaluating their safety and efficacy, and comparing their efficacy to other emerging therapeutic approaches potentially for SM-induced tissue injury in the eye, lung, and skin.
Topics: Mustard Gas; Exosomes; Skin; Stem Cells; Sulfur; Chemical Warfare Agents
PubMed: 37373093
DOI: 10.3390/ijms24129947 -
Toxicology Letters Jun 2021Sulfur mustard (SM) is a chemical warfare agent that has been used throughout recent history and remains a threat today. Exposed soldiers and civilians experience a... (Review)
Review
Sulfur mustard (SM) is a chemical warfare agent that has been used throughout recent history and remains a threat today. Exposed soldiers and civilians experience a variety of symptoms primarily in the respiratory system, skin, and eyes. The ocular tissues are highly sensitive to damage by SM and undergo unique manifestations of acute, chronic, and delayed complications that can persist for months and years after exposure. The mechanisms of this unique mustard gas keratopathy are still not fully understood and animal models for the study of this disease are discussed. Recent advances in mechanisms of injury are included in this review. Ophthalmic manifestations of SM injury including persistent epithelial defects, limbal stem cell deficiency, corneal neovascularization, dry eye, and corneal opacification have been reported. A wide variety of medical and surgical therapies have been studied and are reviewed here along with potential future therapies.
Topics: Chemical Warfare Agents; Drug Administration Schedule; Eye Diseases; Humans; Mustard Gas
PubMed: 33600921
DOI: 10.1016/j.toxlet.2021.02.007 -
Asian Pacific Journal of Cancer... 2015Catastrophic effects of mustard gas as a chemical warfare agent have always been a major problem for those exposed to this agent. In this meta-analysis it was tried to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Catastrophic effects of mustard gas as a chemical warfare agent have always been a major problem for those exposed to this agent. In this meta-analysis it was tried to evaluate carcinogenesis, ocular, cutaneous and respiratory complications of mustard gas exposure among Iranians who had been exposed to this agent during the Iran-Iraq war.
MATERIALS AND METHODS
In this meta-analysis, the required data were collected using keywords "mustard gas", "sulfur mustard", "cancer", "neoplasm", "respiratory complications", "ocular complications" , "lung disease", "chronic complication", "eye", "skin", "cutaneous complication", "carcinogenesis" and their combination with keywords "Iran", "Iranian", "prevalence", "mortality" and their Farsi equivalent terms from the databases of SID, Iranmedex, Magiran, Pubmed, Science Direct, Google Search engine, Gray Literature and Reference of References. To determine the prevalence of each complication and perform meta-analysis, CMA: 2 (Comprehensive Meta-Analysis) software with a randomized model was used.
RESULTS
Of the 542 articles found, 7 national articles, consistent with the aims of this study were selected. Meta- analysis of seven papers revealed that cancer risk, especially cancer of the respiratory system was elevated, so that the relative risk (RR) of cancer role of mustard gas was inconsistent from 2/1 to 4 in this survey. Also prevalence of delayed skin disorders due to sulfur mustard was 94.6%, pulmonary complications 94.5% and ocular complications 89.9%. The incidence of various cancers in victims exposed to mustard gas was 1.7% worldwide where the rate was 2.2% in Iranian victims of the Iraq-Iran war.
CONCLUSIONS
Based on present study the prevalence of delayed mustard gas related cutaneous, pulmonary and ocular complications is above 90% and risk of carcinogenesis is higher in comparison to worldwide statistics. This may suggest need for long-term and persistent follow-up and rehabilitation procedures for populations exposed to this agent.
Topics: Carcinogenesis; Chemical Warfare Agents; Eye; Eye Neoplasms; Humans; Iran; Iraq; Lung; Lung Neoplasms; Mucous Membrane; Mustard Gas; Skin; Skin Neoplasms
PubMed: 26625763
DOI: 10.7314/apjcp.2015.16.17.7567 -
Caspian Journal of Internal Medicine 2022Amongst the chemical warfare agents, blistering (vesicant) agents can be significant materials. The most important agent in this group is sulfur mustard (mustard gas)... (Review)
Review
BACKGROUND
Amongst the chemical warfare agents, blistering (vesicant) agents can be significant materials. The most important agent in this group is sulfur mustard (mustard gas) which is known as "King of chemical warfare (CW) agents ". Exposure to this agent, seriously causes damages in several organs, such as the eyes. This article reviews the ophthalmological aspects of sulfur mustard with reference of its management.
METHODS
A wide-ranging search in PubMed databases, Thomson Reuters and Scopus was done and different aspects of chemical properties of sulfur mustard, its mechanism of action and effects on eyes, clinical finding, diagnostic evaluation, initiate actions, pharmaceutical and surgical interventions was reported.
RESULTS
Sulfur mustard can alkylate DNA and RNA strands and break down structures of protein and lipid of cell membrane. This may impair cell energy production, and leads to cell death. Exposure to sulfur mustard, therefore, causes such problems for organs, including irreversible damage to the eyes.
CONCLUSION
Understanding the mechanism of the sulfur mustard effect and the early training in prevention injuries will cause fewer complications and damage to organs, including the eyes. Washing the eyes with tap water or eyewash solutions, using mydriatic drops, anti- inflammatory drugs, matrix metalloproteinase inhibitors and antibiotics may help to the management of poisoning. Surgical interventions including tarsorrhaphy, amniotic membrane transplantation, stem cell transplantation and corneal transplantation could reduce the harm to the victims.
PubMed: 35974928
DOI: 10.22088/cjim.13.3.458 -
The Journal of Pharmacology and... Jan 2024Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical... (Review)
Review
Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation to crowd control and chemical warfare, and acute exposure can induce lasting respiratory complications. The intentional release of chemical warfare agents (CWAs) during World War I caused life-long damage for survivors, and CWA use is outlawed by international treaties. However, in the past two decades, chemical warfare use has surged in the Middle East and Eastern Europe, with a shift toward lung toxicants. The potential use of industrial and agricultural chemicals in rogue activities is a major concern as they are often stored and transported near populated areas, where intentional or accidental release can cause severe injuries and fatalities. Despite laws and regulatory agencies that regulate use, storage, transport, emissions, and disposal, inhalational exposures continue to cause lasting lung injury. Industrial irritants (e.g., ammonia) aggravate the upper respiratory tract, causing pneumonitis, bronchoconstriction, and dyspnea. Irritant gases (e.g., acrolein, chloropicrin) affect epithelial barrier integrity and cause tissue damage through reactive intermediates or by direct adduction of cysteine-rich proteins. Symptoms of CWAs (e.g., chlorine gas, phosgene, sulfur mustard) progress from airway obstruction and pulmonary edema to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which results in respiratory depression days later. Emergency treatment is limited to supportive care using bronchodilators to control airway constriction and rescue with mechanical ventilation to improve gas exchange. Complications from acute exposure can promote obstructive lung disease and/or pulmonary fibrosis, which require long-term clinical care. SIGNIFICANCE STATEMENT: Inhaled chemical threats are of growing concern in both civilian and military settings, and there is an increased need to reduce acute lung injury and delayed clinical complications from exposures. This minireview highlights our current understanding of acute toxicity and pathophysiology of a select number of chemicals of concern. It discusses potential early-stage therapeutic development as well as challenges in developing countermeasures applicable for administration in mass casualty situations.
Topics: Humans; Lung; Chlorine; Chemical Warfare Agents; Phosgene; Acute Lung Injury; Irritants
PubMed: 37863486
DOI: 10.1124/jpet.123.001822 -
Archives of Iranian Medicine Apr 2020War causes more death and disability than many major diseases. There are few studies in the context of the deleterious impact of war on fertility potential; therefore,... (Review)
Review
BACKGROUND
War causes more death and disability than many major diseases. There are few studies in the context of the deleterious impact of war on fertility potential; therefore, in this study, we tried to review articles about the adverse effects of war on male/ female fertility potential.
METHODS
In this study, a total of 183 articles related to the effects of war on fertility potential were examined by a systematic search using known international medical databases.
RESULTS
Among these studies, there were limited studies on the effects of war on female infertility and most studies examined the effects of war on sperm parameters and male infertility. The physical and psychological trauma of war can increase the risk of infertility in men and women. Presence of reproductive system toxins in weapons, stressful periods of war and direct damage to the reproductive system can impair the fertility of men and women. The way war affects male fertility is not clear, but the higher degree of stress during wartime seems to play an important role. Using reproductive toxicants during the war also increases the risk of impairment in reproductive function in men. Some studies have shown the harmful effects of Sulfur mustard as a war chemical toxin especially on sperm quality and male infertility. Oxidative stress induced by free radicals is a major mechanism for the direct effects of Sulfur mustard on male infertility.
CONCLUSION
The study of past research suggests that exposure to war may be an independent risk factor for reproductive disorders and infertility in men. For female infertility, war leads to menstrual dysfunction.
Topics: Chemical Warfare Agents; Female; Fertility; Free Radicals; Humans; Infertility, Female; Infertility, Male; Male; Mustard Gas; Oxidative Stress; Risk Assessment; War-Related Injuries
PubMed: 32349503
DOI: 10.34172/aim.2020.s4 -
Toxicology and Applied Pharmacology Aug 2016Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment... (Review)
Review
Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant.
Topics: Animals; Chemical Warfare Agents; Fibrin; Humans; Irritants; Lung; Lung Injury; Matrix Metalloproteinases; Mesenchymal Stem Cells; Mustard Gas; RNA, Untranslated; Reactive Nitrogen Species; Reactive Oxygen Species; Transforming Growth Factor beta; Transient Receptor Potential Channels; Tumor Necrosis Factor-alpha
PubMed: 27212445
DOI: 10.1016/j.taap.2016.05.014 -
Cornea Jun 2023Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to... (Review)
Review
PURPOSE
Mustard gas (MG) is a potent blistering and alkylating agent that has been used for military and terrorism purposes. Ocular surface injuries are common after exposure to MG. This review provides an update on the pathophysiology, ocular surface complications, and treatment options for MG-related ocular injuries.
METHODS
Required information was obtained by reviewing various databases such as Cochrane Library, Google Scholar, and PubMed until March 2022. Data were collected by using keywords: "mustard gas" OR "sulfur mustard" AND "eye" OR "cornea" OR "ocular complication" OR "keratitis" OR "keratopathy" OR "limbal stem cell deficiency" OR "dry eye."
RESULTS
Chronic intracellular toxicity, inflammation, and ischemia have been shown to play an essential role in the pathogenesis of MG injury. Ocular surface injuries can have acute, chronic, and most distinctly a delayed-onset presentation leading to various degrees of limbal stem cell deficiency. To date, no treatment has been agreed on as the standard treatment for chronic/delayed-onset MG keratopathy. Based on the authors' experience, we propose a management algorithm for MG-related ocular surface injuries involving optimization of ocular health, anti-inflammatory therapy, and if needed surgical interventions. The management of chronic and delayed-onset presentation remains challenging.
CONCLUSIONS
MG keratopathy is a unique form of chemical injury which can lead to a range of ocular surface pathologies. Long-term anti-inflammatory therapy even in patients with seemingly mild disease may potentially reduce the likelihood of the development of more severe delayed-onset disease.
Topics: Humans; Mustard Gas; Chemical Warfare Agents; Cornea; Corneal Diseases; Eye Injuries
PubMed: 36729713
DOI: 10.1097/ICO.0000000000003182 -
Annals of the New York Academy of... Nov 2020Exposure to vesicants, including sulfur mustard and nitrogen mustard, causes damage to the epithelia of the respiratory tract and the lung. With time, this progresses to... (Review)
Review
Exposure to vesicants, including sulfur mustard and nitrogen mustard, causes damage to the epithelia of the respiratory tract and the lung. With time, this progresses to chronic disease, most notably, pulmonary fibrosis. The pathogenic process involves persistent inflammation and the release of cytotoxic oxidants, cytokines, chemokines, and profibrotic growth factors, which leads to the collapse of lung architecture, with fibrotic involution of the lung parenchyma. At present, there are no effective treatments available to combat this pathological process. Recently, much interest has focused on nutraceuticals, substances derived from plants, herbs, and fruits, that exert pleiotropic effects on inflammatory cells and parenchymal cells that may be useful in reducing fibrogenesis. Some promising results have been obtained with nutraceuticals in experimental animal models of inflammation-driven fibrosis. This review summarizes the current knowledge on the putative preventive/therapeutic efficacy of nutraceuticals in progressive pulmonary fibrosis, with a focus on their activity against inflammatory reactions and profibrotic cell differentiation.
Topics: Animals; Chemical Warfare Agents; Dietary Supplements; Disease Models, Animal; Humans; Irritants; Mechlorethamine; Mustard Gas; Pulmonary Fibrosis
PubMed: 32725637
DOI: 10.1111/nyas.14442