Alterations of Gene Expression in Sulfur Mustard‐Exposed Skin Topically Treated with Vanilloids

Sabourin, Carol L.; Rogers, James V.; Stonerock, Mindy K.; Niemuth, Nancy A.; Kiser, Robyn C.; Casbohm, Stacy L.; Babin, Michael C.; Schlager, John J.; Casillas, Robert P.

doi:10.1081/cus-200041508

Cited by 11 publications

(8 citation statements)

References 21 publications

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“…The sprouting of endothelial cells and formation of new blood vessels (angiogenesis) was noticed at 7 days post‐SM exposure. SM‐induced skin lesions observed in untreated control mice in this study confirms the general pattern of injury and healing as described in the previous studies in the same animal model by us and in other mammalian species in other studies …”

Section: Discussionsupporting

confidence: 83%

A novel decontaminant and wound healant formulation of N,N′‐dichloro‐bis[2,4,6‐trichlorophenyl]urea against sulfur mustard–induced skin injury

Lomash

Pant

2014

Wound Repair Regeneration

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Sulfur mustard (SM)-induced dermatotoxicity can be prevented by an immediate use of decontamination agents. However, practically due to the time lapse between decontamination and exposure, there is always a possibility of wound formation. In view of this, a hydrophilic decontamination formulation of CC-2 (DRDE/WH-03) was fortified with Aloe vera gel and betaine (DRDE/WH-01) for improving its wound healing ability. Swiss albino mice were exposed to SM percutaneously (5 mg/kg) once, and after 24 hours, DRDE/WH-01, DRDE/WH-03, framycetin, and aloe gel were applied topically, daily for 7 days. Skin sections were subjected to histopathology, histomorphologic grading, tissue leukocytosis, and immunohistochemistry of inflammatory-reparative biomarkers on 3 and 7 days, respectively. DRDE/WH-01, framycetin, and aloe gel showed better reepithelialization, angiogenesis, and fibroplasia compared with DRDE/WH-03 and SM control. On the basis of histomorphologic scale, DRDE/WH-01, framycetin, and aloe gel were found to be equally efficacious. Up-regulation of interleukin-6 and infiltrating leukocytes, endothelial nitric oxide synthase and angiogenesis, fibroblast growth factor, and transforming growth factor-alpha with fibroplasia and reepithelialization were well correlated at various stages of the healing process. DRDE/WH-01 was equally effective as framycetin and has shown improved wound healing efficacy compared with DRDE/WH-03. Thus, DRDE/WH-01 can be recommended as a universal decontaminant and wound healant against vesicant-induced skin injury.

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Section: Discussionsupporting

confidence: 83%

A novel decontaminant and wound healant formulation of N,N′‐dichloro‐bis[2,4,6‐trichlorophenyl]urea against sulfur mustard–induced skin injury

Lomash

Pant

2014

Wound Repair Regeneration

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“…We have recently demonstrated the use of mRNA expression as a tool for evaluating the effect of the anti-inflammatory compounds olvanil, octyl homovanillamide, and heptyl isovanillamide against SM injury [9,65]. The findings from the present study may serve as an initial screen for additional biomarkers to evaluate the efficacy of medical treatments against SM injury.…”

Section: Discussionmentioning

confidence: 73%

Microarray analysis of gene expression in murine skin exposed to sulfur mustard

Rogers

Choi

Kiser

et al. 2005

J. Biochem. Mol. Toxicol.

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The chemical warfare agent sulfur mustard [bis-(2-chloroethyl)-sulfide; SM] produces a delayed inflammatory response followed by blister formation in skin of exposed individuals. Studies are underway evaluating the efficacy of pharmacological compounds to protect against SM skin injury. Microarray analysis provides the opportunity to identify multiple transcriptional biomarkers associated with SM exposure. This study examined SM-induced changes in gene expression in skin from mice cutaneously exposed to SM using cDNA microarrays. Ear skin from five mice, paired as SM-exposed right ear and dichloromethane vehicle-exposed left ear at six dose levels (0.005, 0.01, 0.02, 0.04, 0.08, and 0.16 mg; 6 mM to 195 mM range), was harvested at 24 h post-exposure. SM-induced gene expression was analyzed using cDNA microarrays that included 1,176 genes. Genes were selected on the basis of all mice (N=5) in the same dose group demonstrating a > or =2-fold increase or decrease in gene expression for the SM-exposed tissue compared to the dichloromethane vehicle control ear tissue at all six SM doses. When skin exposed to all six concentrations of SM was compared to controls, a total of 19 genes within apoptosis, transcription factors, cell cycle, inflammation, and oncogenes and tumor suppressors categories were found to be upregulated; no genes were observed to be downregulated. Differences in the number and category of genes that were up- or down-regulated in skin exposed to low (0.005-0.01 mg) and high (0.08-0.16 mg) doses of SM were also observed. The results of this study provide a further understanding of the molecular responses to cutaneous SM exposure, and enable the identification of potential diagnostic markers and therapeutic targets for treating SM injury.

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“…Edema can be quantified by measuring 8-mm-diameter ear punch biopsy weights. This model has been used to screen many compounds and remains the most cost-effective live animal screen available (Casillas et al, 2000a,b;Dachir et al, 2002Dachir et al, , 2004aBabin et al, 2003;Casbohm et al, 2004;Sabourin et al, 2004;Wormser et al, 2004aWormser et al, ,b, 2005Kiser et al, 2005;Amitai et al, 2006;Dillman et al, 2006). These effects occur in a dose-dependent manner (Figure 39.4).…”

Section: Model Systems For Screening Smmentioning

confidence: 99%