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Sulfur mustard (SM) is an alkylating and forming chemical that was widely used by Iraqi forces during the Iran-Iraq wars. One of the target organs of SM is the skin. Understanding the mechanisms involved in the pathogenesis of SM may help better identify complications and find appropriate treatments. The current study collected ten SM-exposed patients with long-term skin complications and ten healthy individuals. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the skin protein profile, and statistical bioinformatics methods were used to identify the differentially expressed proteins. One hundred twenty-nine proteins had different expressions between the two groups. Of these 129 proteins, 94 proteins had increased expression in veterans' skins, while the remaining 35 had decreased expression. The hub genes included RPS15, ACTN1, FLNA, HP, SDHC, and RPL29, and three modules were extracted from the PPI network analysis. Skin SM exposure can lead to oxidative stress, inflammation, apoptosis, and cell proliferation., (© 2022. The Author(s).)

The mustard lung is a late consequence of exposure to sulfur mustard (SM) in veterans who had participated in the Iraq-Iran war. Three mechanisms are contributed in the pathogenesis of mustard lung including oxidative stress, protease-antiprotease imbalance, and dysregulated immune response. In the context of the immune response, the role of the inflammasome complex and their inflammatory cytokines are important. This study aims to investigate the inflammasome pathway and their inflammatory cytokine (i.e IL-1 and IL-18) in the peripheral blood of mustard lung patients as well as chronic obstructive pulmonary disease (COPD) patients. This research was conducted as a cross-sectional analytical study on 15 SM patients and was compared with 15 COPD patients and 15 healthy controls. The real-time polymerase chain reaction was used to assess gene expression levels of inflammasome components (NLRP1, NLRP3, NLRC4, and ASC), inflammatory cytokines (IL-1β, IL-18, and IL-1βR), and IL-37 as an anti-inflammatory cytokine. Finally, the data were analyzed by SPSS version 21 software. The gene expression level of molecules involved in inflammasome pathway showed a slight increase in the peripheral blood of SM and COPD patients compared to the control group. However, this difference was not statistically significant. Only IL-37 and NLRP1 had a significant increase in mustard lung and COPD patients; compared to healthy controls (p<0.05). Due to the normal expression of genes involved in the inflammasome pathway, it can be stated that the inflammasome pathway is not active in the blood of mustard lung patients.

Sulphur mustard is an alkylating agent that reacts with different cellular components, causing acute and delayed complications that may remain for decades after exposure. This study aimed to identify differentially expressed metabolites between mustard-exposed individuals suffering from chronic complications compared with unexposed individuals as the control group. Serum samples were obtained from 15 mustard-exposed individuals and 15 apparently healthy unexposed individuals. Metabolomic profiling was performed using (1)H nuclear magnetic resonance spectroscopy, and analyses were carried out using Chenomex and MATLAB softwares. Metabolites were identified using Human Metabolome Database, and the main metabolic pathways were identified using MetaboAnalyst software. Chemometric analysis of serum samples identified 11 differentially expressed metabolites between mustard-exposed and unexposed groups. The main pathways that were influenced by sulphur mustard exposure were related to vitamin B6 (down-regulation), bile acid (up-regulation) and tryptophan (down-regulation) metabolism. Metabolism of vitamin B6, bile acids and tryptophan are the most severely impaired pathways in individuals suffering from chronic mustard-induced complications. These findings may find implications in the monitoring of exposed patients and identification of new therapeutic approaches., (© 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Pulmonary problems are among the most common chronic complications of sulfur mustard (SM) intoxication and adversely affect patients' quality-of-life. The present trial investigated the impact of immunotherapy with interferon (IFN)-γ on quality-of-life, respiratory symptoms, and circulating immunologic and oxidative parameters in patients suffering from chronic SM-induced complications. Patients (n = 15) were administered IFNγ (100 μg) every other day for a period of 6 months. Assessment of quality-of-life [using St. George respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT) indices], the severity and frequency of respiratory symptoms, and serum levels of immunologic [including interleukin (IL)-2, IL-4, IL-6, IL-10, IFNγ, calcitonin gene related peptide (CGRP), matrix metallopeptidase (MMP)-9, and tumor necrosis factor (TNF)-α], oxidative stress [malondialdehyde (MDA) as well as total and reduced glutathione, and catalase and superoxide dismutase (SOD) activity], and fibrogenic [transforming growth factor (TGF)-β] parameters were performed at baseline and at trial end. The results indicated that IFNγ therapy is associated with improvements in SGRQ (p < 0.001) and CAT (p < 0.001) scores, decreased severity of cough (p = 0.001), dyspnea (p < 0.001), and morning dyspnea (p < 0.001), reduced frequency of sputum production (p < 0.001) and hemoptysis (p < 0.001), and elevated FEV1 (p = 0.065). Serum levels of IL-4 (p < 0.001), IL-6 (p < 0.001), IL-10 (p < 0.001), CGRP (p < 0.001), MMP-9 (p = 0.001), TNFα (p < 0.001), TGFβ (p < 0.001) and MDA (p = 0.001) were decreased while those of IL-2 (p < 0.001), IFNγ (p < 0.001), and both total (p = 0.005) and reduced glutathione (p = 0.061) increased by the end of the trial. It was concluded that IFNγ has favorable effects on the quality-of-life and alleviates respiratory symptoms in patients suffering from chronic SM-induced pulmonary complications. A modulation of cytokines and oxidative stress appears responsible for the clinical efficacy of IFNγ.

Background: Chronic cutaneous complications such as pruritus are among the very frequent complaints of sulphur mustard (SM)-exposed patients. The present trial investigated the impact of curcumin on serum inflammatory biomarkers and their association with pruritus severity and quality of life (QoL)., Methods: This was a randomized, double-blind trial among 96 male Iranian veterans (age 37-59 y) who were suffering from chronic SM-induced pruritic skin lesions. Patients were randomly assigned to curcumin (1 g/d, n = 46) or placebo (n = 50) for four weeks. Serum concentrations of interleukins 6 (IL-6) and 8 (IL-8) together with high-sensitivity C-reactive protein (hs-CRP) and calcitonin gene-related peptide (CGRP) were measured at baseline and at the end of the trial. Assessment of pruritus severity was performed using the pruritus score and QoL using the Dermatology Life Quality Index (DLQI)., Results: Serum IL-8 and hs-CRP were significantly reduced in both groups but the magnitude of reduction was greater in the curcumin group (P < 0.001). Serum CGRP was only decreased in the curcumin group (P < 0.001). No significant change was observed in serum IL-6. There were significant correlations between CGRP and IL-6 changes (P = 0.011) and between DLQI and IL-8 changes (P = 0.026) in the curcumin group. In the curcumin group, changes in serum IL-8 concentrations were found as the significant predictor of DLQI scores (P = 0.026) but none of the independent variables could predict pruritus scores., Conclusions: Curcumin supplementation effectively mitigates inflammation in patients suffering from chronic SM-induced cutaneous complications. This anti-inflammatory effect might account for the observed pruritus alleviation and QoL improvement by this phytochemical.

Background: Eyes are the most sensitive organs to sulfur mustard (SM). Late ocular complications have been reported even 15-20 years post-exposure. To date, no study has investigated the composition of tear proteins in tear samples of SM-intoxicated patients., Methods: Total protein content as well as concentrations of vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and substance P were measured in unstimulated tears of chemically-injured patients who suffer from late ocular complications of SM. These levels were compared to corresponding values obtained from tears of healthy control subjects. The concentration of total proteins was measured using the Bradford method and those of VEGF, CGRP and substance P by ELISA., Results: Total protein concentration was significantly lower in tears of the SM compared to control group (p<0.01). In contrast, tear samples of the SM group had significantly higher VEGF and VEGF/total protein compared to control group (p<0.01). Tear CGRP concentration was found to be lower in the SM vs. control group (p<0.05) but no significant difference in CGRP/total protein was observed (p>0.05). Finally, tear substance P concentrations were not found to be significantly different between the two groups (p>0.05)., Conclusion: The results of this investigation indicated decreased total protein and CGRP, and elevated VEGF concentration in tears of SM-intoxicated patients who suffer from chronic ocular complications.

Understanding the molecular and cellular mechanisms involved in the pathogenesis of ocular injured induced by mustard gas can help better identify complications and discover appropriate therapies. This study aimed to analyze the proteomics of tears of chemical warfare victims with mustard gas ocular injuries and compare it with healthy individuals. In this case-control research, 10 mustard gas victims with long-term ocular difficulties (Chronic) were included in the patient group, while 10 healthy persons who were age and sex matched to the patients were included in the control group. Schirmer strips were used to collect the tears of the participants. Proteomics experiments were performed using the high-efficiency TMT10X method to evaluate the tear protein profile, and statistical bioinformatics methods were used to identify the differently expressed proteins. 24 proteins had different expressions between the two groups. Among these 24 proteins, 8 proteins had increased expression in veterans' tears, while the remaining 16 proteins had decreased expression. Reactome pathways were used to look at proteins with various expressions, and 13 proteins were found to be engaged in the immune system, 9 of which were effective in the innate immune system, and 5 proteins were effective in the complement cascade. Ocular mustard gas exposure may cause a compromised immune system on the eye's surface, exposing the cornea to external and endogenous infections, and eventually causing corneal opacity and reduced vision. [ABSTRACT FROM AUTHOR]

The mustard lung is a late consequence of exposure to sulfur mustard (SM) in veterans who had participated in the Iraq-Iran war. Three mechanisms are contributed in the pathogenesis of mustard lung including oxidative stress, protease-antiprotease imbalance, and dysregulated immune response. In the context of the immune response, the role of the inflammasome complex and their inflammatory cytokines are important. This study aims to investigate the inflammasome pathway and their inflammatory cytokine (i.e IL-1 and IL-18) in the peripheral blood of mustard lung patients as well as chronic obstructive pulmonary disease (COPD) patients. This research was conducted as a cross-sectional analytical study on 15 SM patients and was compared with 15 COPD patients and 15 healthy controls. The real-time polymerase chain reaction was used to assess gene expression levels of inflammasome components (NLRP1, NLRP3, NLRC4, and ASC), inflammatory cytokines (IL-1β, IL-18, and IL-1βR), and IL-37 as an anti-inflammatory cytokine. Finally, the data were analyzed by SPSS version 21 software. The gene expression level of molecules involved in inflammasome pathway showed a slight increase in the peripheral blood of SM and COPD patients compared to the control group. However, this difference was not statistically significant. Only IL-37 and NLRP1 had a significant increase in mustard lung and COPD patients; compared to healthy controls (p<0.05). Due to the normal expression of genes involved in the inflammasome pathway, it can be stated that the inflammasome pathway is not active in the blood of mustard lung patients. [ABSTRACT FROM AUTHOR]

Sulfur Mustard (SM), a cytotoxic vesicant chemical warfare agent, has powerful irritant and blistering effects on the skin, eyes and respiratory tract. Since during the Iraq-Iran war, many Iranian soldiers and civilians were exposed to SM, there are several victims still suffering from long-term cutaneous, ocular and pulmonary complications. Currently, there is no definite treatment for long-term complications of SM, and only supportive medical care is being taken to minimize the symptoms. In this study, we compared the cost-effectiveness of common drugs that are used against long-term SM-induced complications in Iranian patients. In this review article, electronic databases were checked using the following key words: sulfur mustard, lung, skin, eye, cost-effectiveness, pharmacoeconomics and treatment. Abstracts of non-English papers and proceedings of congresses on SM were also assessed. Among the studied drugs, high-dose oral N-acetyl cysteine and long-acting inhaled corticosteroids against respiratory complications, topical corticosteroids and oral antihistamines against cutaneous complications and non-steroidal anti-inflammatory drugs and corticosteroids ophthalmic drops against ocular complications were found to be cost-effective. Usage of different drugs in the treatment of SM injuries in Iran, have imposed a significant economic burden to patients and their families because many drugs that are effective against chemical injuries are not covered by insurance. In addition, the development of more effective drugs in this field is considered as an urgent demand that should be noticed by the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Sulphur mustard is an alkylating agent that reacts with different cellular components, causing acute and delayed complications that may remain for decades after exposure. This study aimed to identify differentially expressed metabolites between mustard-exposed individuals suffering from chronic complications compared with unexposed individuals as the control group. Serum samples were obtained from 15 mustard-exposed individuals and 15 apparently healthy unexposed individuals. Metabolomic profiling was performed using ¹H nuclear magnetic resonance spectroscopy, and analyses were carried out using Chenomex and MATLAB softwares. Metabolites were identified using Human Metabolome Database, and the main metabolic pathways were identified using MetaboAnalyst software. Chemometric analysis of serum samples identified 11 differentially expressed metabolites between mustard-exposed and unexposed groups. The main pathways that were influenced by sulphur mustard exposure were related to vitamin B6 (down-regulation), bile acid (up-regulation) and tryptophan (down-regulation) metabolism. Metabolism of vitamin B6, bile acids and tryptophan are the most severely impaired pathways in individuals suffering from chronic mustard-induced complications. These findings may find implications in the monitoring of exposed patients and identification of new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Respiratory disorders in sulfur mustard (SM)-exposed and chronic obstructive pulmonary disease (COPD) patients are mostly associated with neutrophilic inflammation, severe airflow limitation, and oxidative stress. The objective of this study was to establish whether neutrophil (PMN) proteomes in these diseases were similar or differed. Blood neutrophil proteomes from healthy, SM-exposed, and COPD subjects were analyzed using two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF MS). Elastase activity was determined kinetically. The results showed that levels of S100 calcium-binding protein (CBP) A12, S100 CBP A8, glyceraldehyde-3-phosphate dehy-drogenase, superoxide dismutase, and protein disulfide isomerase proteins - as well as elastase activity - were significantly increased in PMN from 'diseased' hosts compared to in cells from healthy controls. In contrast, coactosin-like protein, RhoGDP dissociation inhibitor, and actin isoforms were significantly decreased in diseased subjects' PMN compared to PMN of healthy controls. Moreover, serpin B1 and coronin-1A were expressed only in PMN of the healthy subjects. Lastly, S100 CBP A9, endoplasmic reticulum (ER)-60 protease, and glutathione- S-transferase isoforms were differentially expressed in the cells from the SM-exposed and COPD subjects. These results show that serpin B1, an efficient inhibitor of neutrophil serine proteases, was not detectable, and elastase activity significantly increased in PMN from both SM-exposed and COPD patients. It seems that, apart from inflammation and oxidative stress, a protease:anti-protease imbalance exists within PMN of both COPD and SM-exposed patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • A pocket sensor has been introduced to monitor the changes in the plasma metabolites. • The sensor was provided by mixing organic dyes and bimetallic nanoparticles. • The sensor was employed to distinguished war veterans injured by sulfur mustard. • It is possible to observe the color changes within 3 min. • The low cost of the fabrication process was provided to use in hospitals and medical centers. A pocket sensor was provided by immobilizing twelve color mixtures containing organic dyes and copper-silver bimetallic nanoparticles coated with dopamine (Dopamine/Ag@Cu BMNPs) on a paper substrate. Due to the catalytic properties of the BMNPs, the index metabolites of the plasma were converted into aldehyde or acid compounds that interacted with the organic dyes. The assay was presented to monitor the changes in the plasma sample's metabolites of 123 injured veteran and 40 healthy people. It is possible to observe the response of sensor with the naked eye within 3 min. To perform this discrimination, the proposed sensor was found to be 87% accurate. The quantitative responses of the sensor were indicated a strong correlation with the severity of the injury. The low cost of the fabrication process, availability, and non-invasiveness of the prepared assay make it an acceptable diagnostic method in hospitals and medical centers. [ABSTRACT FROM AUTHOR]