Characterization of acute and long-term sulfur mustard-induced skin injuries in hairless guinea-pigs using non-invasive methods.
OBJECTIVE
Skin exposure to sulfur mustard (HD) results in erythema, edema and severe injury, which take long time to heal and might impose a heavy burden on the health system. Despite many years of research, there is no treatment that prevents the development of the cytotoxic effects of HD causing acute and prolonged damage to the skin. Therefore, it is of great importance to develop treatments that will ameliorate the extent of injury and improve as well as shorten the healing process. The aim of the present study was to establish a small animal model for a long-term HD-induced skin injury using the hairless guinea-pig (HGP) and to further test the efficacy of anti-inflammatories in ameliorating the pathology.


METHODS
HGPs were exposed to HD vapor on four sites for various time durations (1, 5, 10, 15 and 30 min). Clinical evaluation was conducted using reflectance colorimetry, transepidermal water loss and wound-area measurements. Biochemical [prostaglandin (PGE) content and metalloproteinase-9 (MMP-9) activity] and histopathological evaluations were conducted up to 2 weeks post-exposure.


RESULTS
Typical symptoms of HD skin injury developed including erythema and edema and the extent of injury was closely related to the exposure duration. Histological evaluation revealed severe edema, infiltration of inflammatory cells, damage to basal cells and vesication. By 2 weeks, healing was not completed, impaired basement membrane and epithelial hyperplasia were observed. PGE content and MMP-9 activity increased at 2 h post-exposure; however, while PGE returned to baseline levels within 24 h, MMP-9 remained elevated at least up to 48 h. Furthermore, a short-term, topical, anti-inflammatory post-exposure treatment was effective in reducing the extent of the acute injury.


CONCLUSIONS
These results indicate that the effects of HD on HGP skin are similar to previously shown effects in the pig model and in humans and therefore support the use of the HGP as an animal model for long-term effects of HD on skin injury and for studying the efficacy of anti-inflammatory treatments.
Dachir
Shlomit
S
Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel. shlomitd@iibr.gov.il
Cohen
Maayan
M
Fishbeine
Eliezer
E
Sahar
Rita
R
Brandies
Rachel
R
Horwitz
Vered
V
Kadar
Tamar
T
D000208:Acute Disease; D000818:Animals; D001706:Biopsy; D001768:Blister / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003877:Dermatitis, Contact / Q000378:metabolism / Q000473:pathology*; D003879:Dermatologic Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D004890:Erythema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006168:Guinea Pigs; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009151:Mustard Gas / Q000633:toxicity*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D014867:Water / Q000378:metabolism
D003879:Dermatologic Agents; D014867:Water; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009151:Mustard Gas