Sulfur mustard-increased proteolysis followingin vitro andin vivo exposures

Cowan, Fred M.; Yourick, Jeffrey J.; Hurst, Charles G.; Broomfield, Clarence A.; Smith, William J.

doi:10.1007/bf00755605

Cited by 36 publications

(13 citation statements)

References 10 publications

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“…A 25-l aliquot of homogenate (12 and 24 h post-exposure) was incubated with 10 l of an inhibitor solution (0.043 mM Boc-Val-Pro-Val P (OPh) 2 ) in 200 l of buffer for 1 h. A 10-l aliquot of 5 mM Boc-Ala-Ala-Ala-SBzl and 10 l of 5 mM DTNB were then added and the hydrolysis rates were monitored at 405 nm for 1 h. Inhibition of tryptase activity by ophenoxybenzoyl-Pro-4-AmPhGly P (OPh) 2 (0.21 mM) was measured under similar conditions except that 10 l of 5 mM Z-Arg-SBzl was used as a substrate.…”

Section: Inhibitor Studiesmentioning

confidence: 99%

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Cutaneous protease activity in the mouse ear vesicant model†

Powers

Kam

Ricketts³

et al. 2001

J. Appl. Toxicol.

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Section: Inhibitor Studiesmentioning

confidence: 99%

“…[2][3][4] The HD-exposed skin homogenate samples showed enhanced elastase and tryptase activities, whereas the chymase and Asp-ase activities in these samples were not increased. 3 In the mouse ear vesicant model, evaluation of the endpoint responses (e.g.…”

Section: Protease Activitiesmentioning

confidence: 99%

Cutaneous protease activity in the mouse ear vesicant model†

Powers

Kam

Ricketts³

et al. 2001

J. Appl. Toxicol.

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“…Most mustard gas induced cytotoxicity has been studied in skin or skin-derived cell lines in vitro [2][3][4][5]. Previously, the cytotoxic effects of mustard gas were reported to be mainly due to DNA alkylation, leading to vascular leakage, leukocyte infiltration, slow death of basal epidermal cells [6], generation of free radicals [7,8], and activation of protein degradation enzymes [9][10][11]. On the basis of this information, several groups investigated the beneficial effects of agents that scavenge free radicals and other oxidant species.…”

Section: Introductionmentioning

confidence: 99%

Prophylactic protection by N‐acetylcysteine against the pulmonary injury induced by 2‐chloroethyl ethyl sulfide, a mustard analogue

Das

Mukherjee

Smith³

et al. 2003

J Biochem & Molecular Tox

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Mustard gas exposure causes adult respiratory distress syndrome associated with lung injury. The purpose of this study was to investigate whether an antioxidant, such as N-acetylcysteine (NAC), has any protective effect. Guinea pigs were given single exposure (0.5-6 mg/kg body weight) of 2-chloroethyl ethyl sulfide (CEES) as a mustard analogue intratracheally and maintained for various lengths of time (1 h to 21 days). Within 1 h of CEES infusion at 4 mg/kg, high levels of tumor necrosis factor alpha (TNF-alpha), ceramides, and nuclear factor kappaB accumulated in lung and alveolar macrophages. Both acid and neutral sphingomyelinases were activated within 4 h. These signal transduction events were associated with alteration in the oxygen defense system. Within 1 h of exposure to CEES (6 mg/kg body weight), there was 10-fold increase in the (125)I-BSA leakage into lung tissue, indicating severe lung injury. Although low level of CEES exposure (0.5 mg/kg body weight) produced symptoms of chemical burn in lung as early as 1 h after exposure, the severity of edema, congestion, hemorrhage, and inflammation increased progressively with time (1 h to 21 days). Feeding of single dose of NAC (0.5 g) by gavage just before the CEES infusion was ineffective to counteract these effects. However, consumption of the antioxidant in drinking water for 3 or 30 days prior to CEES exposure significantly inhibited the induction of TNF-alpha, activation of neutral and acid sphingomyelinases, production of ceramides, activation of caspases, leakage of (125)I-bovine serum albumin ((125)I-BSA) into lung tissue, and histological alterations in lung. Pretreatment with NAC for 3 and 30 days protected against 69-76% of the acute lung injury. Therefore, NAC may be an antidote for CEES-induced lung injury.

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“…Many in vivo studies have focused on euthymic hairless guinea pig [86][87][88] guinea pig, weanling pig (showing skin lesions similar to humans), rabbit, mouse ear vesicant model 89,90 or various mouse species (nude mice, euthymic hairless mouse etc.) as reviewed by Gerecke 91 , et.…”

Section: Models Systems For Screening Sm Toxicitymentioning

confidence: 99%

Sulphur Mustard Induced Toxicity, Mechanism of Action and Current Medical Management

Pant

Lomash

2016

Def. Life. Sc. Jl.

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Sulphur mustard (SM), chemically, bis (2-chloroethyl) sulphide is a bifunctional alkylating agent that causes cutaneous blisters in human or animals. It was first used in the World War I. Since then, there have been 11 conflicts where SM allegedely had caused mass distruction. Additionally, discarded weapons and stockpiles periodically come to surface during agricultural or fishing activities leading to serious injury. Concerns for threat to modern societies by the serious effects of SM, agreements to ban its production and the use has been made as per 1993 chemical weapons convention (CWC) and agent destruction programs. This short review attempts to discuss the histroy, chemical nature, mechanism of toxicity, toxicokinetics, animal models used for SM induced skin and systemic lesions, pathogenesis of SM induced lesions including medical countermeasures for SM toxicity.

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Sulfur mustard-increased proteolysis followingin vitro andin vivo exposures

Cited by 36 publications

References 10 publications

Cutaneous protease activity in the mouse ear vesicant model†

Cutaneous protease activity in the mouse ear vesicant model†

Prophylactic protection by N‐acetylcysteine against the pulmonary injury induced by 2‐chloroethyl ethyl sulfide, a mustard analogue

Sulphur Mustard Induced Toxicity, Mechanism of Action and Current Medical Management

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