Characterization of acute and long-term pathologies of superficial and deep dermal sulfur mustard skin lesions in the hairless guinea pig model.
Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measurements. Prostaglandin E(2)  content, matrix metalloproteinase-2 and 9 activity, and histopathology were conducted up to 4 weeks post-exposure. Sulfur mustard skin injury, including erythema and edema, impairment of skin barrier and wounds developed in a dose-dependent manner. Prostaglandin E(2)  content and matrix metalloproteinase-2 and 9 activities were elevated during the wound development and the healing process. Histological evaluation revealed severe damage to the epidermis and deep dermis and vesications. At 4 weeks postexposure, healing was not completed: significantly impaired stratum corneum, absence of hair follicles, and epidermal hyperplasia were observed. These results confirm the use of the superficial and deep dermal skin injuries in the hairless guinea pigs as suitable models that can be utilized for the investigation of the pathological processes of acute as well as long-term injuries. These models will be further used to develop treatments to improve the healing process and prevent skin damage and long-term effects.
Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel. shlomitd@iibr.gov.il
Shlomit
S
Dachir
Maayan
M
Cohen
Dikla
D
Kamus-Elimeleh
Eliezer
E
Fishbine
Rita
R
Sahar
Rellie
R
Gez
Rachel
R
Brandeis
Vered
V
Horwitz
Tamar
T
Kadar
D000208:Acute Disease; D000279:Administration, Cutaneous; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002908:Chronic Disease; D020405:Dermis / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced*; D004890:Erythema / Q000139:chemically induced*; D006168:Guinea Pigs; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009151:Mustard Gas / Q000633:toxicity*; D011458:Prostaglandins E / Q000378:metabolism; D012869:Skin Absorption; D013997:Time Factors; D014945:Wound Healing
D002619:Chemical Warfare Agents; D011458:Prostaglandins E; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009151:Mustard Gas