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Abstract: Sulfur mustard is one of the chemical warfare agent. It rapidly reacts with the cutaneous tissues and other tissues, leading to various devastating long-term effects on human health. Mustard-exposed veterans suffer from its chronic skin problems, including itching, burning sensation, and eczema. We aimed to evaluate the protective effects of Myrtus communis L. (myrtle) on chronic skin lesions and quality of life of sulfur mustard-exposed veterans. In this randomized, double-blind clinical trial, 60 sulfur mustard-exposed patients were evaluated. Thirty patients received myrtle essence 5% cream (case group) and 30 patients received Eucerin cream (placebo group) twice in a day for one month. Then, We assessed the chronic skin problems and itching-related parameters (such as the itching time, severity, distribution, frequency, and calculated itching score), duration of sleep, number of waking up at night, and quality of life in the both groups. Our analysis of data revealed that application of myrtle cream effectively decreased skin problems including; itching and burning sensation. Additionally, myrtle markedly decreased skin lesion symptoms such as excoriation in the case group as compared with before treatment. Noticeably, myrtle cream significantly improved quality of life of the patients in the case group. The present study provides more in-depth information regarding the protective role of myrtle on the sulfur mustard-induces skin complication. Also, myrtle effectively improved quality of life of the sulfur mustard-exposed veterans.
Subject(s)
Humans , Middle Aged , Skin Diseases/chemically induced , Plant Extracts/therapeutic use , Chemical Warfare Agents/toxicity , Myrtus communis/therapeutic use , Phytotherapy , Mustard Gas/toxicity , Pruritus/chemically induced , Quality of Life , Veterans , Indicators of Quality of Life , Eczema/chemically induced , War Exposure/adverse effects , IranABSTRACT
Objective To establish an animal model of SM by equal toxicity dose(1LD50)-induced acute pulmonary injury in rats and compare the differences of inflammatory factor and protein expression. Methods Rats were randomly divided into five groups. ELISA and immunohistochemical methods were measured. Results Serum INF-γ and IL-23 levels in the intraperitoneal SM group were increased compared with the tracheal SM group;there were also significant differences in serum IL-4 levels between the two groups. In the alveolar septum , the positive expression ratios of NF-Kβ1,NF-Kβp65,ERK,JNK,and p38MAPK in the intraperitoneal SM group were increased compared with the tracheal SM group. Conclusion Using SM (1LD50),There are significantly higher serum inflammatory factor levels and protein-related expression in the alveolar septum of rats intraperitoneally injected with SM compared with those administered SM by intratracheal instillation. The results suggest that pulmonary inflammatory reactions associated with SM are dependent on the route of exposure.
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Chemical warfare agents and chemical terrorism agents have been identified as one of the major threats to human survival and national security currently. The key to dealing with these threats is the effective medical countermeasures of which specific antidotes take center stage. In the past decade,real or potential chemical threats which has sparked regional conflicts,terrorist activities or chemical accidents intentionally or unintentionally have increased the investment in antidotes research and development worldwide. Here,we introduced the research status on medical countermeasures against chemical threat by giving an overview of the United States ″Countermeasures Against Chemi?cal Threats(CounterACT)Program″,and then the recent research progress in antidotes against nerve agents,sulfur mustard and cyanide toxicities were reviewed.
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Vesicants are the main agents used to fill chemical weapons, and chemical weapons abandoned by the Japa-nese Army in China.The mustard-lewisite mixture, which was developed for cold weather or high-altitude use due to its lower freezing point, is a special and important agent.The toxicology, emergency treatment and clinical management of mustard-lewisite mixture poisoning are introduced in this paper.
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Sulphur mustard (SM) is a corrosive alkylating agent that is likely to be absorbed in vivo through the lungs,eyes and skin into internal organs. SM not only can produce its peculiar cytotoxic?ity thought to be mediated by the alkylation of DNA,protein and nucleic acids,but is a strong mutagen and carcinogen. However,whatever the way SM poisoning occurs,lungs are the most vulnerable, and early death is mainly carused by both the acute respiratory distress syndrome and pulmonary infec?tion. In this review,we analyzed SM-induced lung injury mechanisms.
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Background: Patients with long-term complications of sulfur mustard (SM) poisoning are often less able to undertake optimum levels of physical activity and adequately control their dietary intake. The aim of present study was to investigate the dietary intake of patients with SM poisoning in comparison to a control group. Methods: The study was undertaken on 55 Iranian male veterans, who had > 25% disabilities due to long-term complications of SM poisoning and 55 men age-matched healthy subjects. A previously validated food frequency questionnaire (FFQ) was used for measuring dietary macro/micro nutrient intake for both groups; and the results were analysed using Dietplan6 software. Results: Analysis of macro/micro nutrients in dietary intakes of the patients versus the controls showed a significantly lower intake of several nutrients including selenium and carbohydrate. On the other hand, the dietary intake of trans-fatty acids and iodine were significantly higher in these patients. Conclusion: Long-term complications of SM poisoning in the Iranian veterans induce both chemical and physical disabilities. Macro/micro nutrient intake in these patients was significantly different in comparison with matched, healthy subjects. Dietary advice for these patients should be strongly recommended to these patients in order to prevent other chronic diseases.
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DRDE-07, a newly synthesized amifostine analog currently under clinical investigation in a phase I trial, is a potent antidote against sulfur mustard toxicity. The purpose of this research was to evaluate the pharmacokinetic profile of DRDE-07 in female Swiss Albino mice after a single oral dose of 400 or 600 mg/kg. The physicochemical properties of DRDE-07, including solubility, pK a, Log P, plasma protein binding and plasma/blood partitioning, were determined to support the pharmacokinetic characterization. DRDE-07 concentration was determined by an HPLC-UV method. The profile of plasma concentration versus time was analyzed using a non-compartmental model. Plasma protein binding was assessed using ultrafiltration. DRDE-07 appeared rapidly in plasma after oral administration with peak plasma levels (C max) observed in less than 15 min. There was a rapid decline in the plasma levels followed by a smaller second peak about 90 min after dosing. The plasma protein binding of DRDE-07 was found to be less than 25% at all concentrations studied. Plasma clearance of DRDE-07 is expected to be ~1.5 fold higher than the blood clearance of DRDE-07. The probable metabolite of DRDE-07 was identified as phenyl-S-ethyl amine.
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Objective: To study the protective effects of olvanil on sulfur mustard (SM)-induced cutaneous injury. Methods: To establish mouse ear model of SM-induced cutaneous injury, KM mice right ears were exposed to 5 μl of 32 g/L or 128 g/LSM, respectively. Then we evaluated the protective effect of olvanil against SM-induced cutaneous injury with these two concentrations. For mice exposed to 32 g/L SM, olvanil (0.125, 0.25 and 0.5 mg/ear, topically) or indometacin (indomethacin, 10 mg/kg, po) were administrated 20 min or 30 min before SM exposure, respectively. After 24 h SM exposure, ear tissue was harvested and weighted, and the histopathological analysis was conducted. Similarly, for mice exposed to 128 g/L SM, olvanil (0.25 mg/ear, topically) or indomethacin (10 mg/kg, po) were administrated, and ear tissue was harvested and weighted. Results: Olvanil significantly inhibited 32 g/L SM-induced ear edema, cutaneous inflammation and necrosis, while no influence were observed on 128 g/L SM-induced cutaneous injury. Conclusion: Olvanil shows remarkable protective effect on cutaneous injury induced by SM of low concentration.
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An on-site method for the determination of sulfur mustard ( SM) was developed based on pinhole shell-isolated nanoparticle-enhanced Raman spectroscopy. By using 0. 1 mol/L MgSO4 as effective agglomeration reagent, more Raman “hot spots” were induced, and thus a limit of detection for SM at 10 μg/L was achieved with a linearity of 10-1000 μg/L and an analytical enhanced factor of 1. 1×106. This method can be directly applied in the measurement of SM in environmental water samples with good sensitivity and reproducibility, and the standard addition recovery was between 88%-114%. Good differentiation of four SM related compounds, 2-chloroethyl ethylsulfide, thiodiglycol, bis-β-chloroethyl sulphoxide and bis-β-chloroethyl sulphone, was also obtained.
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Objective To establish the sulfur mustard (SM ) induced tracheal injury model in rat and to investigate its mecha-nism .Methods Male rats (SD) were anesthetized and intra-tracheally intubated .The SM group was intra-tracheally injected by 2 mg/kg of diluted SM ,while the propylene glycol control group only by 0 .1mL of propylene glycol and the normal control group had no any treatment .The tissue and blood samples were taken for conducting the HE and immunohistochemical staining and measuring serum enzymes and andinflammatory factors .Results In the SM group ,a large number of lymphocytes infiltration in submucosa were observed;the positive expression of caspase-3 and caspase-9 were observed in epithelium and submucosa ;serum levels of TNF-α,IL-1β,IL-6 reached the peak in 24 h;serum levels of LDH ,GP ,BARS reached the peak in 6h ,so did GGT in 24 h .In the propyl-ene glycol control group and the normal control group ,lymphocytes ,macrophages and neutrophils were rare in submucosa .Conclu-sion The mechanism of SM (2 mg/kg) induced acute tracheal injury involves the inflammatory reaction ,apoptosis and oxidative stress ,moreover the lesion degree has the correlation with time .
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A sensitive determination method for sulfur mustard ( HD ) metabolites thiodiglycol ( TDG ) in rabbit urine was established and validated using isotope dilution negative ion chemical ionization ( NICI) gas chromatography-mass spectrometry ( GC-MS ) , in which deuterated thiodiglycol ( TDG-d8 ) was used as internal standard. Two solid-phase extraction ( SPE) steps were established and optimized in order to reduce the interfering backgrounds, one was used to extract thiodiglycol ( TDG ) from urine with self-assemblied Florisil SPE cartridges, another cleaning treatment of the by-products after pentafluorobenzoyl chloride (PFBZ) derivatization. The results showed that the limits of detection quantitation of this method were 0. 1 and 0. 3 μg/L, respectively. The exposure time-response relationship and exposure dose-response relationship of TDG in rabbit urine were studied after rabbit skin exposure to sulfur mustard (HD, 0. 02-0. 15 LD50). The TDG levels in the rabbit urine increased rapidly during the first day after application and then decreased over time for all dosage groups. A secondary release was also noted for the high-dose group, and the duration of high TDG excretion levels was correlated positively with the HD dosage levels. We thus concluded that abnormally high levels of TDG in urine could be used as a clear diagnostic indicator of HD exposure.
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Sulfur mustard [bis (2-chloroethyl) sulfide, sulfur mustard, SM] is considered a powerful chemical warfare agent.There is still no specific antidote due to its complex toxicological mechanism .An intimate knowledge of the toxic mechanisms and pathophysiological changes is important to the treatment of sulfur mustard injury .Oxidative stress is one of the most important pathophysiological processes involved in the toxic effect of sulfur mustard .The study of oxidative stress biomarkers induced by sulfur mustard can help to reveal the role of oxidative stress in sulfur mustard intoxication , which may contribute to better understanding of the toxic mechanism and development of therapeutic measures after sulfur mustard exposure.The research advances in oxidative stress biomarkers in sulfur mustard intoxication are reviewed .
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Aims and Objectives: We evaluated the incidence of coronary artery disease (CAD) in Sulfur mustard (SM) exposed veterans. We also evaluated the relationship between exposure to SM and angiography findings and compared angiography findings of SM exposed individuals with unexposed ones after two decades from the time of exposure to SM. Materials and Methods: A case-control study was conducted on 200 consecutive patients (100 SM exposed vs. 100 unexposed) undergoing angiographic assessments due to CAD. Results: The coronary angiography findings between two groups were significantly different ( P < 0.001). Ninety two (92%) patients in SM exposed group and 82 (82%) in unexposed group had abnormal findings in their coronary arteries ( P = 0.031). Conclusions: The incidence of CAD and angiographic changes were significantly increased with exposure to SM. Further studies on cardiovascular effects of SM are needed.
Subject(s)
Chemical Warfare Agents/poisoning , Coronary Angiography , Coronary Disease/chemically induced , Coronary Disease/diagnostic imaging , Female , Humans , Iran , Lung Injury/chemically induced , Male , Middle Aged , Mustard Gas/poisoning , VeteransABSTRACT
Objective To investigate the effect of oxygen free radical (OFR) on the injury of small intestine in rats treated with burn, sulfur mustard or sulfur mustard plus burn. Methods Totally 95 SD rats were randomly divided into four groups: 30 rats subjected to 30 third-degree TBSA scalding (B), 30 injected subcutaneously with 2 ml/kg sulfur mustard (S), 30 subjected to both (SB), 5 as normal controls (C). Activity of diamine oxidase (DAO) and superoxide dismutases (SODs), contents of malonaldehyde (MDA) in plasma, and pathological changes of ileum at 2, 6, 12, 24, 48, 72 h after injury were observed. Results Three treatments could induce significant decrease of activity of SODs (P
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Objective To investigate the damaging effect of sulfur mustard on the mitochondria in rat lymphocytes in vitro.Methods Rat spleen lymphocytes were isolated by density gradient centrifugation and cultured with 100 ?mol/L sulfur mustard in vitro.DNA ladderring was used to detect the cell apoptosis.Cyt-c release was measured by Western blotting.The mitochondria function was detected by MTT method.Fluorescent probe labeled with Rhodamine 123 was used to study mitochondria potential.Results The mitochondria potential and cell viability decreased at 4 h after treated with 100 ?mol/L sulfur mustard.There was a liner correlation between the mitochondria potential and cell viability in lymphocytes.The content of Cyt-c increased significantly at 4 h as compared with control group in Western blotting.Conclusion Sulfur mustard could damage the rat lymphocyte mitochondria significantly,and mitochondria participates in cytotoxic effect induced by the sulfur mustard.
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Objective To detect the mutagenicity of sulfur mustard in the tk gene of L5178Y3.7.2c tk +/- mouse lymphoma cells. Methods The plating efficiency and the mutant frequency were detected by the microtiter procedure. Results Sulfur mustard induced tk locus mutation with mutation frequency 2-15 times higher than that of spontaneous mutation frequency of L5178Y3.7.2c tk +/- cells. There were two different phenotypes of mutation colonies induced, which were large and small colonies, but most of them were small colonies. Conclusion Sulfur mustard is characterized by marked mutagenic activity and cytotoxicity. The compound may result in large range of DNA damage.
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Objective To investigate the changes of caspase 3 activity and the interventional effect of tetrapeptide AC DEVD CHO on sulfur mustard induced apoptosis of lymphocyte. Methods The activity of caspase 3 was detected by fluorospectrophotometry. DNA ladder and apoptosis were detected by DNA agarose gel electrophoresis and flow cytometry. Results Sulfur mustard enhanced the activity of caspase 3 and its polypeptide inhibitor (AC DEVD CHO) partially blocked apoptosis, which was mainly presented as an obscure phenomenon of DNA ladder and a decrease in percentage of apoptosis. Conclusion Sulfur mustard can induce the apoptosis of lymphocyte by means of activating caspase 3. The inhibitor may have an interventional effect on lymphocyte apoptosis induced by sulfur mustard.
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Objective To investigate the manner and molecular mechanism of lymphocyte cytotoxic action induced by sulfur mustard. Methods Lymphocytes were separated from the spleen of Wistar rats and were cultured. DNA strand breaks were detected by fluorospectrophotometry. RT PCR and Western blotting were employed to detect the gene and protein expressions of caspase 3 and its activation. Results Sulfur mustard induced DNA strand breaks in the lymphocytes. Gene and protein expressions of caspase 3 were increased in a time dependent manner. Conclusion Sulfur mustard induces lymphocyte cytotoxic action by means of depending on the expression and activation of caspase 3.
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Objective To study the changes of IL 2 and IL 6 levels and lymphocyte DNA damage in peripheral blood of dog intoxicated by sulfur mustard. Methods Chongqing dogs were subcutaneously injected with sulfur mustard at the dose of 16 mg/kg. Lymphocytes and serum were isolated from dog peripheral blood at different time points as designed. The IL 2 and IL 6 levels in blood serum were measured by radioimmunoassay and lymphocyte DNA damage represented as comet tail length was determined by single cell gel electrophoresis (SCGE). Results Four hours after administration of sulfur mustard, the serum IL 2 and IL 6 levels dogs injected with sulfur mustard decreased and reached the lowest level at 72 h. A significant recovery was found at the time point of 120 h. SCG revealed sulfur mustard induced DNA fragmentation (comet) in dog peripheral lymphocytes. The rate of the damaged lymphocytes and the degree of DNA fragment migration began to increase at 4 h and progressively increased from 24 h to 72 h after sulfur mustard treatment. Conclusion Sulfur mustard intoxication induces early and long lasting decreases in serum IL 2 and IL 6 levels and lymphocyte DNA fragmentation in dog peripheral blood.
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Objective To investigate the apoptotic effect induced by sulfur mustard on the lymphocytes of the rat spleen,and define the role of caspase-3 during the process.Methods Sulfur mustard was given by intraperitoneal injection in a dose of 3.5mg/kg.The animals were anesthetized and the spleens were harvested at different timepoints after intoxication.The histopathogy of spleen was studied with hematoxylin-eosin staining.Caspase-3 mRNA was detected with RT-PCR.Protein expression of caspase-3 was assayed with Western blotting,lymphocytes of rat spleen were isolated and cultured in vitro and they were challenged with sulfur mustard(100?mol/L).The effect of Ac-DEVD-CHO(a specific inhibitor of caspase-3)on sulfur mustard-induced apoptosis of the lymphocytes cultured in vitro was evaluated.Fluorescent probe labeled with Rhodamine 123 was used to study mitochondrial potential.Results The histology of rat spleen was affected after sulfur mustard intoxication,as evidenced by apoptosis of a part of lymphocytes.Protein and mRNA expressions of caspase-3 were increased significantly in the spleens of intoxicated rats as compared with that in control group.DNA ladder and 'sub-G1' peak of lymphocytes which were treated with sulfur mustard in vitro were partially improved by Ac-DEVD-CHO(the specific inhibitor of caspase-3).In addition,mitochondrial potential decreased in a time-dependent manner in the lymphocytes intoxicated by sulfur mustard in vitro compared with that in the control group.Conclusions The spleen is injured in the rat which is intoxicated by sulfur mustard.Lymphocyte apoptosis is one of the mechanisms splenic injury.Caspase-3 may be involved in the process of lymphocyte apoptosis induced by sulfur mustard.