Sulfur mustard downregulates iNOS expression to inhibit wound healing in a human keratinocyte model

Ishida, Hiroshi; Ray, Radharaman; Ray, Prabhati

doi:10.1016/j.jdermsci.2007.09.002

Cited by 24 publications

(19 citation statements)

References 23 publications

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“…of HD were assayed by cyclic voltammetry. The data correlate with study carried out by Ishida et al (2008). They proposed that HD could also downregulate an important enzyme participating in infl ammation: inducible nitric oxide synthase.…”

Section: Estimate Of Hd Impact On Organismsupporting

confidence: 85%

Shift of oxidants and antioxidants levels in rats as a reaction to exposure to sulfur mustard

Pohanka

Štětina

2009

J of Applied Toxicology

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Antixodants as well as oxidants levels were investigated in plasma of rats exposed to sulfur mustard in doses of 0 (control), 5, 20 and 80 mg kg(-1) body weight. Cyclic voltammetry performed on screen-printed strips with platinum working electrode used as a tool for assaying oxidant and antioxidant levels. We found significant shifts in both examined analytes. A dose of sulfur mustard of 5 mg kg(-1) body weight caused only a small change in oxidant and antioxidant levels when compared with the control group. A dose of 20 mg kg(-1) body weight provided a significant increase in antioxidants as well oxidants; however, the ratio of both was similar to that in the control group. The most surprising facts were found when the highest dose of 80 mg kg(-1) body weight of sulfur mustard was applied. While antioxidants were significantly increased, oxidants were decreased on an extensive scale.

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Section: Estimate Of Hd Impact On Organismsupporting

confidence: 85%

Shift of oxidants and antioxidants levels in rats as a reaction to exposure to sulfur mustard

Pohanka

Štětina

2009

J of Applied Toxicology

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“…Interestingly, an investigation of hydrogen peroxide production by leukocytes in fixed-frozen tissue sections of HD-induced skin inflammation revealed that agents that modulate NO production by NOS or NOS inhibitors failed to affect H 2 O 2 content (Dannenberg et al, 1994). Furthermore, Ishida et al (2008) demonstrated that application of HD down-regulated iNOS expression in a human keratinocyte model. It should be noted that in the short repertoire of publications concerning the involvement of the nitrergic system in HD-evoked injuries there is no demonstration of actual enzyme activity or NO formation.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide induced protection against sulfur mustard cytotoxicity in RAW264.7 cells through generation of TNF-.ALPHA.

et al. 2010

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-Sulfur mustard (HD), a very potent alkylating agent and lipopolysacchride (LPS), are both well characterized inflammatory factors. We have found that concomitant exposure of murine macrophage cells (RAW264.7) to LPS and HD induced protection against HD induced cytotoxicity. Both HD and LPS induce release of inflammatory markers in RAW264.7 cells. However, there are marked differences in the repertoire of inflammatory factors released by the two toxins: While exposure to HD, induced a dose-dependant death of these cells, no significant change in survival rate was observed following LPS (1-100 ng/ml) exposure. Additionally, LPS elicited a robust nitric oxide (NO) and TNF-α secretion whereas HD was practically ineffective. Both toxins increased PGE 2 secretion in a concentration dependent manner. Treatment of HD-exposed RAW264.7 cells with anti-inflammatory drugs such as dexamethazone (5 μM), voltaren (diclofenac) (8 μM) or doxycycline (5 μM), decreased the release of cytokines but had no effect on cell viability. Simultaneous application of LPS (100 ng/ml) and HD (20-100 μM) resulted in an amelioration of HD cytotoxicity. Adding the NO generator S-nitrosoglutathione (GSNO) or inhibiting NO production using L-N G -monomethyl Arginine, had no effect on cell viability. Moreover, addition of PGE 2 (20 ng/ml) failed to induce any changes in cell viability under basal or HD-induced toxicity. In contrast, TNF-α (20 ng/ml) provided remarkable protection against HD-induced cell death. These findings strongly suggest that LPS exerts its protective action against HD toxicity through the generation of TNF-α and may provide better understanding of the mechanism of cytoprotection.Key words: Sulfur mustard, RAW 264.7, LPS, TNF-α, NO, Cytotoxicity Correspondence: Nahum Allon (E-mail: nahuma@iibr,gov.il) Original ArticleThe Journal of Toxicological Sciences (J. Toxicol. Sci.) Vol.35, No.3, 345-355, 2010 Vol. 35 No. 3 345 Similarly, cutaneous application of HD is also associated with an acute inflammatory response accompanied by blister formation and epithelial necrosis (Dannenberg et al., 1985;Casillas et al., 2000;Dachir et al., 2002). Notably, early studies using isolated skin explants treated with HD have shown a rapid production of cytokines and prostaglandins (Rikimaru et al., 1991).In vitro studies, where the effects of adjacent tissue are absent, have indicated that HD exposure can directly induce cytokine secretion from macrophages as shown in various cells in culture including in human monocytes (Rikimaru et al., 1991;Arroyo et al., 1995). A number of cell lines such as macrophages (Amir et al., 1998, monocytes (Arroyo et al., 1995), lymphocytes and keratinocytes (Arroyo et al., 2000), show acute reaction to HD, similar to that reported in in-vivo studies, and thus, can serve as a model. These studies showed that HD can induce the release of TNFα and other inflammatory mediators by direct action on epithelial cells, suggesting that an inflammatory response can be initiated directly by HD in a single cell (Dan...

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“…A reduction in cell migration would have an effect on wound healing and it has been shown that wounds are slower to heal in SM burns than in a comparable thermal burn [29]. It has also been recently shown that SM affects cell migration in human keratinocyte cells [6].…”

Section: Actinmentioning

confidence: 99%

“…Other features of SM exposure include the build up of necrotic and apoptotic cells and a recruitment of inflammatory cells including neutrophils. Delayed cell migration has also been observed in vitro [6]. Although the pathology of SM-induced injuries takes hours to days to appear there will be immediate effects on the cell after SM exposure, which are likely to be at the molecular level.…”

Section: Introductionmentioning

confidence: 98%

Direct binding of sulfur mustard and chloroethyl ethyl sulphide to human cell membrane-associated proteins; implications for sulfur mustard pathology

Sayer¹,

Whiting²,

Green³

et al. 2010

Journal of Chromatography B

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Sulfur mustard downregulates iNOS expression to inhibit wound healing in a human keratinocyte model

Cited by 24 publications

References 23 publications

Shift of oxidants and antioxidants levels in rats as a reaction to exposure to sulfur mustard

Shift of oxidants and antioxidants levels in rats as a reaction to exposure to sulfur mustard

Lipopolysaccharide induced protection against sulfur mustard cytotoxicity in RAW264.7 cells through generation of TNF-.ALPHA.

Direct binding of sulfur mustard and chloroethyl ethyl sulphide to human cell membrane-associated proteins; implications for sulfur mustard pathology

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