Mustard Gas Inhalation Injury

Keyser, Brian M.; Andres, Devon; Holmes, Wesley W.; Paradiso, Danielle; Appell, Ashley; Letukas, Valerie A.; Benton, Betty; Clark, Offie; Gao, Xiugong; Ray, Prabhati; Anderson, Dana R.; Ray, Radharaman

doi:10.1177/1091581814532959

Cited by 24 publications

(17 citation statements)

References 88 publications

(128 reference statements)

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“…Isolating a single mechanism of toxicity for SM is difficult because its high reactivity allows it to alkylate many cellular macromolecules that in turn can affect many biological processes. Many diverse therapies have been tested as countermeasures against SM toxicity including anti-inflammatory drugs, antioxidants, protease inhibitors, and anti-apoptotic compounds (Keyser et al, 2014;Tang and Loke, 2013;Weinberger et al, 2011). These treatments have been met with mixed results, and the search continues to find a feasible drug therapy for use in treating humans exposed to SM.…”

Section: Discussionmentioning

confidence: 99%

“…A hindrance in developing treatments for SM inhalation is due to our poor understanding of its pathogenesis. Previous studies suggest that SM induces oxidative stress, inflammation, apoptosis, DNA damage, and airway coagulation that are all known to play a role in damage progression (Keyser et al, 2014). Many therapeutics targeting these pathways have been tested and have shown some promise in in vitro models (Weinberger et al, 2011).…”

mentioning

confidence: 99%

“…susceptible to SM toxicity, with the majority of historical mortality being attributed to pulmonary injury (Keyser et al, 2014). Inhaled SM may cause death or the development of severe chronic airway disorders in survivors (Poursaleh et al, 2012).…”

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confidence: 99%

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From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity

et al. 2016

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Sulfur mustard (bis 2-chloroethyl ethyl sulfide, SM) is a powerful bi-functional vesicating chemical warfare agent. SM tissue injury is partially mediated by the overproduction of reactive oxygen species resulting in oxidative stress. We hypothesized that using a catalytic antioxidant (AEOL 10150) to alleviate oxidative stress and secondary inflammation following exposure to SM would attenuate the toxic effects of SM inhalation. Adult male rats were intubated and exposed to SM (1.4 mg/kg), a dose that produces an LD 50 at approximately 24 h. Rats were randomized and treated via subcutaneous injection with either sterile PBS or AEOL 10150 (5 mg/kg, sc, every 4 h) beginning 1 h post-SM exposure. Rats were euthanized between 6 and 48 h after exposure to SM and survival and markers of injury were determined. Catalytic antioxidant treatment improved survival after SM inhalation in a dose-dependent manner, up to 52% over SM PBS at 48 h post-exposure. This improvement was sustained for at least 72 h after SM exposure when treatments were stopped after 48 h. Non-invasive monitoring throughout the duration of the studies also revealed blood oxygen saturations were improved by 10% and clinical scores were reduced by 57% after SM exposure in the catalytic antioxidant treatment group. Tissue analysis showed catalytic antioxidant therapy was able to decrease airway cast formation by 69% at 48 h post-exposure. To investigate antioxidant induced changes at the peak of injury, several biomarkers of oxidative stress and inflammation were evaluated at 24 h post-exposure. AEOL 10150 attenuated SM-mediated lung lipid oxidation, nitrosative stress and many proinflammatory cytokines. The findings indicate that catalytic antioxidants may be useful medical countermeasure against inhaled SM exposure.Key words: sulfur mustard; chemical weapons; antioxidant.Sulfur mustard (SM) is a chemical warfare agent possessing strong alkylating properties that induces inflammation and tissue necrosis. SM exposure produces delayed and highly incapacitating injuries that can be lethal (Anderson, 2015). SM was used during World War I and is still maintained in the chemical weapons arsenals of several countries (Kehe and Szinicz, 2005). A specific and effective antidote is not available for use after SM exposure despite research conducted for nearly 100 years (Kehe and Szinicz, 2005). The population most at risk for exposure to SM is comprised of soldiers and individuals working or living near storage depots, but SM is also considered to be a potential terrorist threat due to its low cost of production and simple synthesis.Sulfur mustard (SM) vapor adversely affects the skin, eyes, and the respiratory tract. The respiratory tract is highly

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Section: Discussionmentioning

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From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity

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“…These CWAs are particularly destructive to the skin, eyes, and lungs where they may cause painful blisters, blindness, edema, and respiratory distress[5]. Vesicating agents are highly toxic, and while exposures to these agents can be lethal, their primary value lies in incapacitating their victims and causing fear [6].…”

Section: 0 Overview Of the Evidence For Oxidative Stress In Cwas Anmentioning

confidence: 99%

“…Another mechanism of SM damage is through interactions with proteins, leading to their alkylation and subsequent inactivation[7]. A third possible mechanism of action is through the depletion of cellular GSH reserves, disrupting the redox equilibrium, causing the initiation of lipid peroxidation cascades and indirectly leading to apoptosis[5,10]. SM sulfonium ions may also be directly reduced by cytochrome P450 reductase to form carbon-based free radicals capable of forming oxygen free radicals[11].…”

Section: 0 Overview Of the Evidence For Oxidative Stress In Cwas Anmentioning

confidence: 99%

Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals

McElroy

Day

2016

Biochemical Pharmacology

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The continuing horrors of military conflicts and terrorism often involve the use of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). Many CWA and TIC exposures are difficult to treat due to the danger they pose to first responders and their rapid onset that can produce death shortly after exposure. While the specific mechanism(s) of toxicity of these agents are diverse, many are associated either directly or indirectly with increased oxidative stress in affected tissues. This has led to the exploration of various antioxidants as potential medical countermeasures for CWA/TIC exposures. Studies have been performed across a wide array of agents, model organisms, exposure systems, and antioxidants, looking at an almost equally diverse set of endpoints. Attempts at treating CWAs/TICs with antioxidants have met with mixed results, ranging from no effect to nearly complete protection. The aim of this commentary is to summarize the literature in each category for evidence of oxidative stress and antioxidant efficacy against CWAs and TICs. While there is great disparity in the data concerning methods, models, and remedies, the outlook on antioxidants as medical countermeasures for CWA/TIC management appears promising.

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Clinical Pharmacology and Toxicology of Mustard Compounds

Ghorani‐Azam

Balali‐Mood

2015

Basic and Clinical Toxicology of Mustard Compounds

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Mustard Gas Inhalation Injury

Cited by 24 publications

References 88 publications

From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity

From the Cover: Catalytic Antioxidant Rescue of Inhaled Sulfur Mustard Toxicity

Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals

Clinical Pharmacology and Toxicology of Mustard Compounds

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