Protective effect of various antioxidants on the toxicity of sulphur mustard administered to mice by inhalation or percutaneous routes

Kumar, Om; Sugendran, K.; Vijayaraghavan, R.

doi:10.1016/s0009-2797(00)00209-x

Cited by 98 publications

(68 citation statements)

References 31 publications

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“…Direct intratracheal administration of tissue plasminogen activator (tPA) has been previously shown to improve survival of animals after exposure to CEES and SM through the reduction of obstructive airway casts. Stoichiometric antioxidants including the water soluble vitamin E analog trolox, and the bioflavonoid quercetin have been shown to improve median survival times in mice exposed to SM (Kumar et al, 2001;Veress et al, 2013Veress et al, , 2015. This is the first published study to report significant improvements in survival using a catalytic antioxidant in a rat model of SM inhalation.…”

Section: Discussionmentioning

confidence: 82%

“…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. One recurring theme in SM toxicity models is the presence of an oxidative stress component which may be responsible for propagating the deleterious effects of SM (Brimfield et al, 2012;Inturi et al, 2011;Jain et al, 2011) 2008; Kumar et al, 2001). It is difficult to compare many of the results of these studies because they occur across many different models of SM exposure, time points, toxicity endpoints, and are often performed with surrogate SM agents such as 2-chloroethyl ethyl sulfide (CEES).…”

Section: Discussionmentioning

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

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Significant decrease in reduced glutathione and increase in the level of malondialdehyde indicated oxidative damage to liver and lung tissues following SM inhalation and percutaneous exposure. Trolox and quercetin protected the liver and lung tissues from oxidative damage caused by SM exposure through inhalation and percutaneous routes (Kumar et al, 2001). Quercetin was administered intraperitoneally to mice along with SM and oxidative stress parameters were evaluated after 7 days.…”

Section: Flavonoids As Promising Cytoprotectants For Sulphur Mustard mentioning

confidence: 99%

“…Oxidative stress is one of the many causes of the mustard agents' toxicity and antidotes directed against them have proven to be beneficial. Antioxidants can enhance survival time, protect liver and lung from oxidative damage and also reduce accumulation of purine metabolites in SM toxicity (Kumar et al, 2001;Vijayaraghavan et al, 2009). Among the various types of nucleophiles, the flavonoids appear to be very promising.…”

mentioning

confidence: 99%

Flavonoid Treatment for Mustard Agents' Toxicity

Vijayaraghavan¹,

Gautam²

2012

Oxidative Stress - Environmental Induction and Dietary Antioxidants

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“…It has been shown that decreased glutathione and increased serum malondialdehyde levels in mustard lung patients can be an indicator of oxidative-antioxidative system imbalance (16). The previous animal model studies have mentioned that the activation of inflammatory cells are involved in the pathogenesis of SM lung injury (19,20).It is well documented that oxidative antioxidative imbalance may result in oxidative stress and triggering inflammatory process (21).…”

Section: Pathogenesismentioning

confidence: 99%