Amelioration of sulfur mustard skin injury following a topical treatment with a mixture of a steroid and a NSAID

Abstract

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.

The use of doxycycline as a protectant against sulphur mustard in HaCaT cells

“…It remains to be determined if the combined use of these compounds with protease inhibitors would be useful adjunct to HD therapy, though Cowan et al (2003) refer to such inhibitors as ethyl p-guanidino benzoate HCl as having potential utility. It is generally the case that anti-inflammatory compounds are more effective in in vivo models than other classes of candidate countermeasures, though such treatments do not prevent epithelial cell death occurring in the skin following exposure to HD (Dachir et al, 2004). This is a finding supported in the present study.…”

Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

“…Early studies with the SM analogs 2-chloroethyl ethyl sulfide (CEES) and NM from our laboratory and elsewhere have shown that pathways related to DNA damage, oxidative stress and inflammation are involved in their skin injury effects (Sabourin et al , 2002; Kehe et al , 2009; Pal et al , 2009; Tewari-Singh et al , 2010; Inturi et al , 2011; Jain et al , 2011a; Jain et al , 2011b). Accordingly, both antioxidants, such as AEOL10150, glutathione, sulforaphane, butylated hyroxyanisole, ebselen and others (Paromov et al , 2007; Laskin et al , 2010; Tewari-Singh et al , 2011; Tewari-Singh et al , 2014a) and anti-inflammatory drugs (Nyska et al , 2001; Dachir et al , 2004; Chang et al , 2014) have been evaluated to treat vesicant-induced skin injuries and have shown some promise. However, more efforts are needed to identify novel agents to rescue vesicants-induced skin injuries, specifically in the mass causality scenario.…”

Chemical Warfare Agents and Risks to Animal Health

“…Topical silver sulfadiazine can be applied to all burns, and an Elizabethan collar should be put in place to decrease ingestion of the ointment and self-trauma. Topically applied dexamethasone and diclofenac reduced inflammation in a mouse when applied within 4 h (Dachir et al, 2004). All equine and ovine patients should be inoculated with tetanus toxoid.…”