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Toxicology Letters Apr 2021The use of sulfur mustard (SM) in global terrorism is still a relevant threat to both civilian population and military personnel. Casualties exposed to SM may present... (Review)
Review
The use of sulfur mustard (SM) in global terrorism is still a relevant threat to both civilian population and military personnel. Casualties exposed to SM may present mild, moderate or severe acute ocular lesions followed by a complete ocular resolution, chronic lesions or re-emerged ocular pathologies after a latent period. Current treatment for SM-induced ocular injury is based mainly on the clinical manifestation at the different stages of the injury and includes pharmaceutical and surgical interventions. These therapeutic measures are beneficial but not sufficient, and the ocular injury remains a continuous challenge for medical professionals. This review focuses on treatment experience carried out in humans and studied in animal models, for both SM-induced ocular acute injury and late pathology. In general, therapeutic measures are based on clinical features of the ocular injury or on the involvement of specific factors during the ocular injury that point out towards potential treatments. Anti-inflammatory treatments and limbal stem cell transplantation techniques were developed based on the clinical manifestation of the ocular injury. Optional therapies for impaired corneal innervation and endothelium are suggested for future research. Additionally, studies on potential treatments with anti-matrix metalloproteinase (MMP), anti-vascular endothelial growth factor (VEGF) and anti-IL-6 agents are discussed. Consequently, future studies may reveal the potential of additional pharmacological and biological treatments or advanced cellular and molecular biology methods to serve as novel therapeutic measures and techniques for this complicated ocular injury.
Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Corneal Transplantation; Eye Injuries; Humans; Models, Animal; Mustard Gas
PubMed: 33440228
DOI: 10.1016/j.toxlet.2021.01.006 -
Expert Review of Clinical Immunology Dec 2017Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with... (Review)
Review
Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung. Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017. Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.
Topics: Airway Obstruction; Airway Remodeling; Animals; Chemical Warfare; Goblet Cells; Humans; Immunomodulation; Immunotherapy; Inflammation; Lung Diseases; Metaplasia; Mustard Gas; Pulmonary Disease, Chronic Obstructive; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 28994328
DOI: 10.1080/1744666X.2017.1389646 -
Archives of Iranian Medicine Sep 2022Sulfur mustard (SM) is a lethal chemical agent that affects many organs, particularly the eyes, respiratory system and skin. Even asymptomatic patients with documented... (Review)
Review
Sulfur mustard (SM) is a lethal chemical agent that affects many organs, particularly the eyes, respiratory system and skin. Even asymptomatic patients with documented SM vapor exposure may develop organ disorder many years later. Patients with even minor signs in the acute stage may experience late complications that necessitate surgery. Early decontamination and conservative measures could help the patients and decrease the complications. Despite decades of research, there is still no effective treatment for either acute or long-term SM-induced ocular complications. Even after multiple medications and surgical procedures, the majority of patients continue to have symptoms. For dry eye, punctual occlusion, autologous eye drops, and aggressive lubrication are used; for persistent epithelial defects (PED), tarsorrhaphy, amniotic membrane transplant, and stem cell transplantation are used; for total limbal stem cell deficiency (LSCD), living-related conjunctivolimbal allograft and keratolimbal allograft are used; for corneal vascularization, steroids, non-steroidal anti-inflammatory drugs, and anti-vascular endothelial growth factor prescribed; and for corneal opacities, corneal transplantation is done. Platelet rich plasma and topical drops containing stem cell transplantation for LSCD, photodynamic therapy paired with subconjunctival or topical anti-vascular endothelial growth factors for corneal vascularization, topical curcumin and topical ciclosporin-A for dry eye, and orbital fat-derived stem cells for PED are all alternative treatments that can be suggested. Despite the experimental and clinical research on the complications of SM exposure over the past decades, there is still no effective treatment for eye complications. However, supportive medical and surgical management has been applied with relatively good outcome.
Topics: Humans; Mustard Gas; Stem Cells; Skin; Treatment Outcome
PubMed: 37543890
DOI: 10.34172/aim.2022.100 -
International Journal of Organ... 2018Tissue engineering and cell-based therapies are promising therapeutic approaches in structural and functional defects of the trachea. Researchers have focused on these... (Review)
Review
Tissue engineering and cell-based therapies are promising therapeutic approaches in structural and functional defects of the trachea. Researchers have focused on these approaches to overcome the complications related to such diseases. Patients exposed to mustard gas suffer from massive damage to the respiratory system. Current treatment plans are only palliative and include anti-inflammatory drugs, broncholytics, long-acting β-agonists, and inhaled corticosteroids. As mustard gas exposure leads to chronic airway inflammation, it seems that tracheobronchomalacia, because of chronic inflammation and weakness of the supporting cartilage, is an important factor in the development of chronic and refractory respiratory symptoms. The previous studies show that regenerative medicine approaches have promising potential to improve the life quality of patients suffering from tracheal defects. It seems that the engineered tracheal graft may improve the respiratory function and decrease symptoms in patients who suffer from asthma-like attacks due to mustard gas exposure. There are several successful case reports on the transplantation of stem cell-based bioartificial grafts in structural airway diseases. Therefore, we hope that the reconstruction of tracheobronchial structure can lead to a decrease in respiratory difficulties in mustard gas-exposed patients who suffer from tracheomalacia. In the present review, we summarize the main aspects of tracheal tissue engineering and cell-based therapies and the possibilities of the application of these approaches in mustard gas-exposed patients.
PubMed: 30863517
DOI: No ID Found -
Journal of Special Operations Medicine... 2019Sulfur mustard has been used in conflicts for more than a century. Despite international recognized bans on the use of chemical weapons, there continue to be reports of... (Review)
Review
Sulfur mustard has been used in conflicts for more than a century. Despite international recognized bans on the use of chemical weapons, there continue to be reports of their use. The authors provide a contemporary overview of sulfur mustard injury and its management in the acute, subacute, and chronic periods.
Topics: Chemical Warfare Agents; Humans; Mustard Gas; Occupational Exposure; Wounds and Injuries
PubMed: 31201756
DOI: 10.55460/DWNJ-ZSVN -
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 -
ACS Applied Materials & Interfaces Nov 2018Sulfur mustard gas, also called HD, is one of the main chemical warfare agents and has claimed thousands of lives and left many more contaminated. The development of...
Sulfur mustard gas, also called HD, is one of the main chemical warfare agents and has claimed thousands of lives and left many more contaminated. The development of functional materials to promptly capture and detoxify sulfur mustard within a few minutes is extremely important to save the lives of the affected people. This has motivated us to explore excellent detoxification systems that can be deployed in the field to rapidly capture and hydrolyze mustard gas in a short time. To that end, we present a silver-ion-exchanged zeolite Y [(Ag) @Y, n = 5, 13, 21, 32, 43, and 55] that can rapidly capture mustard gas and its simulant (2-chloroethyl ethyl sulfide, CEES) in ambient conditions to enable the prompt hydrolysis of the CEES captured in its nanopores. The capture and hydrolysis ability of Ag@Y positively correlated with its number of Ag ions. In addition, 70% of CEES (2.5 μL in 1 mL) was captured by (Ag)@Y within 20 min at 25 °C in ambient conditions. Moreover, 100% CEES (2.5 μL in 1 mL aqueous ethanol cosolvent) was hydrolyzed in 1 min at 25 °C. The efficiency of Ag@Y in capturing and hydrolyzing CEES as well as mustard gas is thus a system with high detoxification efficiency for this dangerous chemical warfare agent.
PubMed: 30375849
DOI: 10.1021/acsami.8b15362 -
Toxicology Jan 2023Sulfur mustard (SM), an extremely reactive alkylating toxicant, which poses a continuing threat to both military and civilian populations. SM targets three major organs... (Review)
Review
Sulfur mustard (SM), an extremely reactive alkylating toxicant, which poses a continuing threat to both military and civilian populations. SM targets three major organs including skin, eyes and lungs. In recent years, more and more clinical findings have shown that cognitive and emotional disorders in veterans intoxicated with SM, such as anxiety, depression, apathy, cognitive decline and so on, which indicated the long time toxic effects on mental and neurological health of SM. The experimental studies in animal and cell models have also found neurotoxicity which are similar to clinical results. However, these neuropsychological problems are not studied well in victims of SM and the mental and neurological complications are often not subjected to treatment or undertreated. Until now, the exact mechanism of the action of SM toxicity has not been elucidated and no specific therapy for its poisoning exists. Therefore, the studies on neurotoxicity of SM should be strengthened. This review summarizes the main progress of clinical and experimental researches on neurotoxicity of SM for the past few years.
Topics: Animals; Mustard Gas; Chemical Warfare Agents; Skin; Eye; Lung; Neurotoxicity Syndromes
PubMed: 36356660
DOI: 10.1016/j.tox.2022.153372 -
Experimental Eye Research Nov 2023Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various...
Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3 μL solution of 0.25 mg/mL or 5 mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5 min. Mice were evaluated prior to and after exposure on days 1, 3, 7, 14, and 28 for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation was used to examine corneal cross-sections collected at the completion of follow-up. Following exposure, mice experienced central corneal epithelial erosion and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma in both dosages. The epithelium was recovered by day 3 in the low dose group, followed by exacerbated punctuate erosions alongside persistent corneal edema that arose and continued onward to four weeks post-exposure. The high dose group showed persistent epitheliopathy throughout the study. The endothelial cell density was reduced, more prominent in the high dose group, early after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at 4 weeks post-exposure included dysmorphic basal epithelial cells and reduced epithelial thickness, and in the limbal cornea included decreased cellular layers. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas.
Topics: Humans; Animals; Mice; Mustard Gas; Mechlorethamine; Cornea; Corneal Diseases; Corneal Edema; Corneal Ulcer; Vision Disorders; Microscopy, Confocal
PubMed: 37722586
DOI: 10.1016/j.exer.2023.109657 -
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