Therapeutic effects of hypothermia on Lewisite toxicity

Nelson, Peggy; Hancock, James R.; Sawyer, Thomas W.

doi:10.1016/j.tox.2005.12.026

Cited by 15 publications

(18 citation statements)

References 21 publications

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“…Since corneal wounding, ulceration, inflammation, neovascularization and their progression were observed clinically and quantified with LEW in this study, examination of related histopathology and mechanisms of acute and long-term corneal injury and healing are now warranted in future. In this regard, it is reported that LEW and SM produce lesions that have similar gross appearance in skin, eye and lungs, but their pathology and development can differ since the mechanism of action of LEW-induced injuries is also associated with arsenic poisoning and inhibition of carbohydrate metabolism (3, 5, 19, 28). Hence, deciphering the mechanism of ocular injuries following LEW exposure would help in outlining the pathways that could be targeted to develop effective therapies against LEW-induced ocular injuries.…”

Section: Discussionmentioning

confidence: 99%

“…LEW was developed as an arsenical vesicant during World War I but was not used; however, stockpiles are known to exist posing a potential threat of its accidental exposure or use as a warfare/terrorist agent (5, 6). For example, the former Soviet Union stockpiled LEW as a weaponized mixture alongside the chemical warfare agent sulfur mustard [bis(2-chloroethyl) sulfide), SM] (7).…”

Section: Introductionmentioning

confidence: 99%

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Clinical progression of ocular injury following arsenical vesicant lewisite exposure

Tewari‐Singh

Croutch

Tuttle

et al. 2016

Cutaneous and Ocular Toxicology

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Ocular injury by lewisite (LEW), a potential chemical warfare and terrorist agent, results in edema of eyelids, inflammation, massive corneal necrosis, and blindness. To enable screening of effective therapeutics to treat ocular injury from LEW, useful clinically-relevant endpoints are essential. Hence, we designed an efficient exposure system capable of exposing up to six New-Zealand white rabbits at one time, and assessed LEW vapor-induced progression of clinical ocular lesions mainly in the cornea. The right eye of each rabbit was exposed to LEW (0.2 mg/L) vapor for 2.5, 5.0, 7.5 and 10.0 min and clinical progression of injury was observed for 28 days post-exposure (dose-response study), or exposed to same LEW dose for 2.5 and 7.5 min and clinical progression of injury was observed for up to 56 days post-exposure (time-response study); left eye served as an unexposed control. Increasing LEW exposure caused corneal opacity within 6 h post-exposure, which increased up to 3 days, slightly reduced thereafter till 3 weeks, and again increased thereafter. LEW-induced corneal ulceration peaked at 1 day post-exposure and its increase thereafter was observed in phases. LEW exposure induced neovascularization starting at 7 days which peaked at 22-35 days post-exposure, and remained persistent thereafter. In addition, LEW exposure caused corneal thickness, iris redness, and redness and swelling of the conjunctiva. Together, these findings provide clinical sequelae of ocular injury following LEW exposure and for the first time establish clinically-relevant quantitative endpoints, to enable the further identification of histopathological and molecular events involved in LEW-induced ocular injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical progression of ocular injury following arsenical vesicant lewisite exposure

Tewari‐Singh

Croutch

Tuttle

et al. 2016

Cutaneous and Ocular Toxicology

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“…The related histopathology and the mechanisms of acute and long‐term corneal injuries by LEW observed in this rabbit corneal injury model are currently being investigated. It is also important to emphasize that, although the ocular lesions from LEW exposure appear to be similar to SM, their pathology and development could be different, as arsenic poisoning and inhibition of carbohydrate metabolism are also involved in LEW‐induced injury . Hence, our ongoing efforts aimed at understanding the mechanism of ocular injuries following LEW exposure will help in outlining the additional pathways that could be targeted to develop effective therapies against LEW‐induced ocular injuries.…”

Section: Development Of Vesicant‐induced Ocular Injury Modelsmentioning

confidence: 99%

Corneal toxicity induced by vesicating agents and effective treatment options

Goswami

Tewari‐Singh

Agarwal

2016

Annals of the New York Academy of Sciences

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The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial (HCE) cells and rabbit corneal organ culture models with the SM analog nitrogen mustard (NM), which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries.

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“…Hypothermia treatment has been shown to reduce Lewisite‐induced skin injury and cutaneous pain. However, the mechanism underlying hypothermia therapy remains unclear . In male hairless guinea pigs, therapeutic cooling of Lewisite‐exposed skin afforded dramatic protection against injury.…”

Section: Countermeasuresmentioning

confidence: 99%

Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals

Srivastavá

Athar

2016

Annals of the New York Academy of Sciences

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Arsenicals are highly reactive inorganic and organic derivatives of arsenic. These chemicals are very toxic and produce both acute and chronic tissue damage. Based on these observations, and considering the low cost and simple methods of their bulk syntheses, these agents were thought to be appropriate for chemical warfare. Among these, the most known agent synthesized and weaponized during World War I (WWI) is Lewisite. Exposure to Lewisite causes painful inflammatory and blistering responses in the skin, lung, and eye. These chemicals also manifest systemic tissue injury following their cutaneous exposure. Although largely discontinued after WWI, their stockpiles are still known to exist in the former Soviet Union, Germany, Italy, the United States, and Asia. Thus, their access by terrorists or accidental exposure could be highly dangerous for humans and the environment. This review summarizes studies which describe the biological, pathophysiological, toxicological, and environmental effects of exposure to arsenicals, with a major focus on cutaneous injury. Studies related to the development of novel molecular pathobiology–based antidotes against these agents are also described.

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Therapeutic effects of hypothermia on Lewisite toxicity

Cited by 15 publications

References 21 publications

Clinical progression of ocular injury following arsenical vesicant lewisite exposure

Clinical progression of ocular injury following arsenical vesicant lewisite exposure

Corneal toxicity induced by vesicating agents and effective treatment options

Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals

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