摘要
Background:One of the most pervasive complications of burn injury is wound progression,characterized by continuous tissue destruction in untreated wounds,which leads to wound infection,inflammation,oxidative stress and excessive scar formation.We determined whether additional tissue destruction could be attenuated with Livionex formulation(LF)lotion,which contains a metal-chelating agent and reduces inflammation in burn wounds.Methods:We subjected male Sprague Dawley rats to a 2%total body surface area(TBSA)burn using a brass comb model and topically applied LF lotion(containing ethylenediaminetetraacetic acid and methyl sulfonyl methane)to the affected area every 8 hours over 3 days.Inflammatory cytokine levels,cell apoptosis and wound healing were compared in LF lotion-treated and untreated rats.Statistical analysis was performed using a one-way analysis of variance in conjunction with Tukey’s post-hoc test.Results:Serum inflammatory cytokines were not detectable after 3 days,suggesting that small burn wounds induce only an immediate,localized inflammatory response.Microscopy revealed that LF lotion improved burn site pathology.Deoxynucleotidyl transferase biotin-d-UTP nick-end labeling staining showed reduced cell death in the LF-treated samples.LF lotion prevented the spread of tissue damage,as seen by increased amounts of Ki-67-positive nuclei in the adjacent epidermis and hair follicles.Tumor necrosis factor-alpha,interleukin-6 and inducible nitric oxide synthase levels in LF-treated skin sections from burned rats were comparable to the levels observed in unburned control sections,indicating that LF lotion reduces inflammation in and around the burn site.Conclusions:These results establish LF lotion as a therapeutic agent for reducing inflammatory stress,cell death and tissue destruction when applied immediately after a burn injury.Further studies of LF lotion on large TBSA burns will determine its efficacy as an emergency treatment for reducing long-term morbidity and scarring.
基金
supported by grants from Livionex Flow through NIH SBIR Phase I,NIAMS(R43 AR062419)
the Army,Navy,NIH,Air Force,VA and Health Affairs to support the AFIRM II effort,under Award No.W81XWH-13-2-0054
The US Army Medical Research Acquisition Activity,820 Chandler Street,Fort Detrick MD 21702–5014 is the awarding and administering acquisition office.Opinions,interpretations,conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.Support was also provided,in part,by National Institute of Environmental Health Sciences(P30 ES006676)
National Institute of General Medical Sciences(P50 GM060338 to DNH and R01 GM112936 to CCF)
Shriners Hospitals for Children(84202 to AE and 80500 to DNH).
