title: Clinically-relevant cutaneous lesions by nitrogen mustard: useful biomarkers of vesicants skin injury in SKH-1 hairless and C57BL/6 mice.
abstract: A paucity of clinically applicable biomarkers to screen therapies in laboratory is a limitation in the development of countermeasures against cutaneous injuries by chemical weapon, sulfur mustard (SM), and its analog nitrogen mustard (NM). Consequently, we assessed NM-caused progression of clinical cutaneous lesions; notably, skin injury with NM is comparable to SM. Exposure of SKH-1 hairless and C57BL/6 (haired) mice to NM (3.2 mg) for 12-120 h caused clinical sequelae of toxicity, including microblister formation, edema, erythema, altered pigmentation, wounding, xerosis and scaly dry skin. These toxic effects of NM were similar in both mouse strains, except that wounding and altered pigmentation at 12-24 h and appearance of dry skin at 24 and 72 h post-NM exposure were more pronounced in C57BL/6 compared to SKH-1 mice. Conversely, edema, erythema and microblister formation were more prominent in SKH-1 than C57BL/6 mice at 24-72 h after NM exposure. In addition, 40-60% mortality was observed following 120 h of NM exposure in the both mouse strains. Overall, these toxic effects of NM are comparable to those reported in humans and other animal species with SM, and thus represent clinically-relevant cutaneous injury endpoints in screening and optimization of therapies for skin injuries by vesicating agents.
authors.affiliation: Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Neera
authors.initials: N
authors.lastname: Tewari-Singh
authors.forename: Anil K
authors.initials: AK
authors.lastname: Jain
authors.forename: Swetha
authors.initials: S
authors.lastname: Inturi
authors.forename: Carl W
authors.initials: CW
authors.lastname: White
authors.forename: Rajesh
authors.initials: R
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D018450:Disease Progression; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004890:Erythema / Q000139:chemically induced / Q000473:pathology; D007509:Irritants / Q000633:toxicity*; D008466:Mechlorethamine / Q000633:toxicity*; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced* / Q000473:pathology*; D012885:Skinfold Thickness; D013997:Time Factors
chemical_list: D015415:Biomarkers; D007509:Irritants; D008466:Mechlorethamine