Clinical and Morphological Findings on Mustard Gas [Bis(2-Chloroethyl)Sulfide] Poisoning

Eisenmenger, Wolfgang; Drasch, G.; Clarmann, M von; Kretschmer, E; Roider, Gabriele

doi:10.1520/jfs13192j

Cited by 85 publications

(55 citation statements)

References 14 publications

(4 reference statements)

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“…SM has been used as a chemical warfare agent in many instances [2][3][4][5] . SM forms sulphonium ion in the body and alkylates DNA leading to DNA strand breaks and cell death 6 .…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Quercetin Against Sulphur Mustard-inducedOxidative Stress in Mice

Gautam¹,

Vijayaraghavan²,

Pant³

et al. 2007

DSJ

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Sulphur mustard (SM) is a chemical warfare agent that causes serious blisters upon contact with human skin. SM alkylates DNA and several other macromolecules, and also induces oxidative stress. Quercetin, a bioflavonoid has wide pharmacological actions. The protective efficacy of quercetin (100 mg/kg, i.p. and 200 mg/kg, i.p.) was studied by administering three doses in mice against SM. The first dose was administered at 30 min prior, simultaneous, 2 h post or 24 h post, and two more doses on the next two days. SM was administered (in PEG 300) percutaneously at varying doses for survival and protection studies. SM was also administered at a dose of 2 LD 50 (19.3 mg/kg) with and without quercetin treatment and various biochemical markers were estimated 7 days after SM administration. Histological examinations of vital organs were also carried out. The animals administered with SM died at various days depending upon the dose. The body weight decreased significantly. Quercetin protected the mice significantly, in a dosedependent manner. The protection was better when the first dose of quercetin administered was 30 min prior or simultaneously. A significant decrease in reduced as well as oxidised glutathione and an increase in malondialdehyde, WBC count, RBC count, and haemoglobin were observed with 2 LD 50 SM. Quercetin at 100 mg/kg and 200 mg/kg doses significantly protected the biochemical markers when the first dose of quercetin administered was 30 min prior or as simultaneous treatment. The histological lesions induced by sulphur mustard on liver, spleen, and skin were also significantly protected by quercetin when the first dose was administered 30 min prior or as simultaneous treatment. The present study shows that percutaneous administration of SM induces oxidative stress and quercetin can protect it as a prophylactic agent.Keywords: Sulphur mustard, quercetin, oxidative stress, glutathione, malondialdehyde, DNA damage, prophylactic agent, chemical warfare agent . INTRODUCTIONThe organophosphorus nerve agents and the blistering agents continue to be threats not only as chemical warfare agents, but also from the terrorist organisations. Though the Chemical Weapons Convention is signed and ratified by several countries and the stockpiled chemical warfare agents are being destroyed, still the threat persists from the Defence Science Journal, Vol. 57, No. 5, September 2007, pp. 707-720 2007, DESIDOC 707 use of chemical weapons. The mechanism of action of the nerve agents is clearly understood and effective and accepted treatment protocols are known 1 . In spite of research over several decades, no satisfactory prophylactic or treatment regimen has evolved for sulphur mustard (SM), a well known blistering agent. So the search for a better antidote is being pursued the world over.

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“…SM has been used as a chemical warfare agent in many instances [2][3][4][5] . SM forms sulphonium ion in the body and alkylates DNA leading to DNA strand breaks and cell death 6 .…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Quercetin Against Sulphur Mustard-inducedOxidative Stress in Mice

Gautam¹,

Vijayaraghavan²,

Pant³

et al. 2007

DSJ

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“…Infection was a dominant feature, as it was among sulfur mustard casualties during the Iran-Iraq conflict in 1984 and 1986. These patients experienced leukopenia accompanied by tctal bone marrow aplasia, wbich included extensive losses of myeloid stem cells Eisenmenger et al, 1991). These findings are further evidence of an association between suppression of immunologic functions and an increased incidence of infectious disease.…”

Section: Veterans At Riskmentioning

confidence: 62%

Veterans at risk: the health effects of mustard gas and Lewisite

1993

Choice Reviews Online

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“…Extracellular signals lead to its translocation into the nucleus where it can bind to gene promoter and/or enhancer sequences and activate the expression of genes involved in the inflammatory and immune response [12,16,17]. Acute pulmonary inflammation, such as is caused by HD inhalation, involves the sloughing of tracheal and bronchial epithelial cells that line the respiratory tract [3]. These cell types may initiate an inflammatory response through the release of mediators that increase vascular permeability and attract blood-borne inflammatory cells.…”

Section: Discussionmentioning

confidence: 99%

“…Large, fluid-filled blisters, characterized by dermal/epidermal separation, occur in humans following percutaneous exposure [1,2]. Inhalation exposure causes toxicity to bronchial epithelial cells that can, if severe enough, lead to bronchopneumonia and death [3,4]. HD is a highly reactive compound that is unstable in biological fluids, making it difficult to quantify the dose received deep in the lungs after an inhalation exposure.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Factor-kappa B is Not Up-Regulated in Rat Pulmonary Tissue Following Sulfur Mustard (HD) Exposure

Danne¹,

Blank²,

Buxton³

et al. 2001

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information SPONSOR/MONITOR'S ACRONYM(S) USAMRICD SPONSOR/MONITOR'S REPORT NUMBER(S)USAMRICD-TR-01-04 DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited SUPPLEMENTARY NOTES ABSTRACTVesicants, such as sulfur mustard (HD), pose an insidious threat to the respiratory tract. Exposure causes acute lung injury characteristic of an inflammatory response. Nuclear Factor-KAPPA B (NF-DB) is a redox sensitive transcription factor important in regulating genes involved in the inflammation. This study evaluated levels of NF-DB following exposure to HD. Male rats were euthanized at 3,6, or 24 hr following intravenous HD or isopropanol (IPA controls) exposure. Nuclear protein samples extracted from pulmonary tissue were analyzed using an electrophoretic mobility shift assay. Bronchoalveolar lavage fluid (BALF) protein concentrations and lactate dehydrogenase (LDH) were determined to indicate lung injury. NF-DB in HD lungs was not detected at a level significantly above that found in IPA samples. LDH was higher than in the IPA-treated group, p<.013, at 24 h. Protein concentrations were higher at 24 h compared with 3 and 6 h, p<.05. In conclusion, i.v. HD causes lung injury at 24 h as measured by BALF protein and LDH low-level inflammatory response related to time but not to dose. This model may be useful in developing anti-inflammatory treatments against HD exposure. These data suggest that alterations in NF-DB may not play a role in HD-induced lung injury in rodents intravenously exposed to HD. SUBJECT TERMSnuclear factor-AAP/M B; sulfur mustard; HD; pulmonary tissue; electrophoretic mobility shift assay, bronchoalveolar lavage fluid, lactate dehydrogenase, protein

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Clinical and Morphological Findings on Mustard Gas [Bis(2-Chloroethyl)Sulfide] Poisoning

Cited by 85 publications

References 14 publications

Protective Effect of Quercetin Against Sulphur Mustard-inducedOxidative Stress in Mice

Protective Effect of Quercetin Against Sulphur Mustard-inducedOxidative Stress in Mice

Veterans at risk: the health effects of mustard gas and Lewisite

Nuclear Factor-kappa B is Not Up-Regulated in Rat Pulmonary Tissue Following Sulfur Mustard (HD) Exposure

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