Amelioration of sulfur mustard skin injury following a topical treatment with a mixture of a steroid and a NSAID.
The ability to ameliorate sulfur mustard (HD)-induced oedema by treatment with anti-inflammatory drugs was reported previously after screening four steroids and four non-steroidal anti-inflammatory drugs (NSAIDs) using the mouse ear vesicant model. Following the screening study, one steroid and one NSAID (Adexone and Voltaren) were selected as the most effective, and a mixture of the two was chosen for the present more extensive research. The effect of the combined treatment on clinical, biochemical and histopathological parameters following HD insult was studied. Mice ears were exposed to 0.2 micro l of HD for 10 min to produce a moderate skin injury. Oedema development peaked ca. 48 h following exposure, as determined by weighing ear biopsies. Histological observations at that time exhibited damage to the epidermis and dermis. An increase in prostaglandin E (PGE) was measured in skin homogenates, starting 8 h following exposure and lasting at least up to 48 h post-exposure. A topical treatment using the above anti-inflammatory mixture significantly reduced inflammatory parameters when applied up to 4 h following exposure. These parameters included extent of oedema, levels of PGE, area of clinical damage and extent of cytotoxic injury (vesications and damaged epithelial cells). Thus, a combination of a steroid and NSAID was found to be effective in reducing the intensity of HD skin injury and possibly shortening the time to full recovery. The treatment, however, did not prevent completely the ensuing cytotoxic processes in the epithelial layer.
Dachir
Shlomit
S
Israel Institute for Biological Research, Department of Pharmacology, PO Box 19, Ness-Ziona 74100, Israel. shlomit@iibr.gov.il
Fishbeine
Eliezer
E
Meshulam
Yakov
Y
Sahar
Rita
R
Chapman
Shira
S
Amir
Adina
A
Kadar
Tamar
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003907:Dexamethasone / Q000627:therapeutic use; D004008:Diclofenac / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004431:Ear, External / Q000187:drug effects / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use*; D007249:Inflammation; D051379:Mice; D008815:Mice, Inbred Strains; D009151:Mustard Gas / Q000008:administration & dosage / Q000633:toxicity*; D011458:Prostaglandins E / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002619:Chemical Warfare Agents; D005938:Glucocorticoids; D011458:Prostaglandins E; D004008:Diclofenac; D003907:Dexamethasone; D009151:Mustard Gas