Time course pathogenesis of sulphur mustard-induced skin lesions in mouse model.
Sulphur mustard (SM) is a bifunctional alkylating agent that causes cutaneous blistering in humans and animals. In this study, we have presented closer views on pathogenesis of SM-induced skin injury in a mouse model. SM diluted in acetone was applied once dermally at a dose of 5 or 10 mg/kg to Swiss albino mice. Skin was dissected out at 0, 1, 3, 6, 12, 24, 48, 72 and 168 hours, post-SM exposure for studying histopathological changes and immunohistochemistry of inflammatory-reparative biomarkers, namely, transforming growth factor alpha (TGF-α), fibroblast growth factor (FGF), endothelial nitric oxide synthase (eNOS) and interlukin 6 (IL-6). Histopathological changes were similar to other mammalian species and basal cell damage resembled the histopathological signs observed with vesication in human skin. Inflammatory cell recruitment at the site of injury was supported by differential expressions of IL-6 at various stages. Time-dependent expressions of eNOS played pivotal roles in all the events of wound healing of SM-induced skin lesions. TGF-α and FGF were strongly associated with keratinocyte migration, re-epithelialisation, angiogenesis, fibroblast proliferation and cell differentiation. Furthermore, quantification of the tissue leukocytosis and DNA damage along with semiquantitative estimation of re-epithelialisation, fibroplasia and neovascularisation on histomorphologic scale could be efficiently used for screening the efficacy of orphan drugs against SM-induced skin injury.
Department of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, India.
Vinay
V
Lomash
Sunil E
SE
Jadhav
Rajagopalan
R
Vijayaraghavan
Satish C
SC
Pant
D000818:Animals; D001707:Biopsy, Needle; D001768:Blister / Q000139:chemically induced* / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009151:Mustard Gas / Q000494:pharmacology* / Q000633:toxicity*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D011897:Random Allocation; D018570:Risk Assessment; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000378:metabolism
D015850:Interleukin-6; D016211:Transforming Growth Factor alpha; D052250:Nitric Oxide Synthase Type III; D009151:Mustard Gas