title: Selection of non-steroidal anti-inflammatory drug and treatment regimen for sulfur mustard-induced cutaneous lesions.
abstract: The inflammatory process plays an important role in sulfur mustard (HD) injury and HD pathogenesis, suggesting that anti-inflammatory treatments applied as soon as possible following HD injury may reduce tissue damage and accelerate healing. This study used the HD dermal weanling swine model to investigate the efficacy of two non-steroidal anti-inflammatory drugs, capsaicin and diclofenac, when applied in combination with the steroid, clobetasol. The therapeutic regimen was also investigated with respect to initiation of treatment post-exposure, frequency and duration. Yorkshire-cross pigs were randomly assigned to experimental groups, corresponding to all combinations of treatment (capsaicin with clobetasol or diclofenac with clobetasol), onset time (1, 2 or 4 h post-exposure), treatment duration (1, 3 or 5 days) and frequency of applications (2, 3 or 4 per day). For each animal, two sites on the ventral abdomen were exposed to 400 μL of neat HD for 8 min to achieve superficial dermal (SD) lesions and two sites were exposed to 400 μL neat HD for 30 min to achieve deep dermal (DD) lesions. Each treatment regimen was tested against a SD and a DD injury. Untreated SD and DD lesion sites served as within-animal controls. Assessments, up to one week post-challenge, included digital photographs, clinical assessments (lesion size measurements and modified Draize scoring), transepidermal water loss (TEWL), reflectance colorimetry and histopathologic evaluations that included an estimate for depth of injury and wound healing parameters. Diclofenac plus clobetasol treatment resulted in significant reductions in lesion contracture and modified Draize scores, increased barrier function (decreased TEWL), and increased healing as determined by histopathology for both SD and DD injury when compared with untreated sites and sites treated with capsaicin plus clobetasol. An increased duration of treatment from 1 to 5 days was most commonly associated with decreased clinical assessment and histopathological severity scores. Therefore, a combination of diclofenac and clobetasol application, when administered for at least five days, shows promise in ameliorating HD-induced lesions.
authors.affiliation: a Battelle , Columbus , OH , USA and.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Plahovinsak
authors.affiliation: a Battelle , Columbus , OH , USA and.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Buccellato
authors.affiliation: a Battelle , Columbus , OH , USA and.
authors.forename: Frances M
authors.initials: FM
authors.lastname: Reid
authors.affiliation: b United States Army Medical Research Institute of Chemical Defense , Aberdeen Proving Ground , MD , USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Graham
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002211:Capsaicin / Q000627:therapeutic use; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002990:Clobetasol / Q000627:therapeutic use*; D004008:Diclofenac / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D009151:Mustard Gas / Q000633:toxicity*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013552:Swine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002619:Chemical Warfare Agents; D004008:Diclofenac; D002990:Clobetasol; D002211:Capsaicin; D009151:Mustard Gas
keywords: Capsaicin; chemical agent; clobetasol; dermal; diclofenac; sulfur mustard; swine; therapy