title: Histopathological and immunohistochemical evaluation of nitrogen mustard-induced cutaneous effects in SKH-1 hairless and C57BL/6 mice.
abstract: Sulfur mustard (SM) is a vesicant warfare agent which causes severe skin injuries. Currently, we lack effective antidotes against SM-induced skin injuries, in part due to lack of appropriate animal model(s) that can be used for efficacy studies in laboratory settings to identify effective therapies. Therefore, to develop a relevant mouse skin injury model, we examined the effects of nitrogen mustard (NM), a primary vesicant and a bifunctional alkylating agent that induces toxic effects comparable to SM. Specifically, we conducted histopathological and immunohistochemical evaluation of several applicable cutaneous pathological lesions following skin NM (3.2mg) exposure for 12-120h in SKH-1 and C57BL/6 mice. NM caused a significant increase in epidermal thickness, incidence of microvesication, cell proliferation, apoptotic cell death, inflammatory cells (neutrophils, macrophages and mast cells) and myleoperoxidase activity in the skin of both mouse strains. However, there was a more prominent NM-induced increase in epidermal thickness, and macrophages and mast cell infiltration, in SKH-1 mice relative to what was seen in C57BL/6 mice. NM also caused collagen degradation and edema at early time points (12-24h); however, at later time points (72 and 120h), dense collagen staining was observed, indicating either water loss or start of integument repair in both the mouse strains. This study provides quantitative measurement of NM-induced histopathological and immunohistochemical cutaneous lesions in both hairless and haired mouse strains that could serve as useful tools for screening and identification of effective therapies for treatment of skin injuries due to NM and SM.
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Jain
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Neera
authors.initials: N
authors.lastname: Tewari-Singh
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Swetha
authors.initials: S
authors.lastname: Inturi
authors.affiliation: Department of Pathology, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Orlicky
authors.affiliation: Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Carl W
authors.initials: CW
authors.lastname: White
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: Rajesh.Agarwal@UCDenver.edu.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001768:Blister / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003877:Dermatitis, Contact / Q000201:enzymology / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008466:Mechlorethamine / Q000633:toxicity*; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D012885:Skinfold Thickness; D013045:Species Specificity
chemical_list: D002619:Chemical Warfare Agents; D008466:Mechlorethamine; D009195:Peroxidase
keywords: C57BL/6 mice; Inflammation; Microblisters; Nitrogen mustard; SKH-1 hairless mice; Skin lesions