James Q. Del Rosso DO FAOCD FAADa,b,c and Leon Kircik MDd,e,f,g
aTouro University Nevada, Henderson, NV, bJDR Dermatology Research Center, Las Vegas, NV, cPrivate Practice,Thomas Dermatology, Las Vegas, NV dIndiana University School of Medicine, Indianapolis, IN eMount Sinai Medical Center, New York, NY fPhysicians Skin Care, PLLC, Louisville, KY gDermResearch, PLLC, Louisville, KY
Escherichia coli, Klebsiella pneumoniae, Enterobacter aero- genes, Pseudomonas aeruginosa, Salmonella typhimurium, Serratia marcescens, Clostridium dif cile, Trichophyton spp, Candida albicans, Leishmania spp, and Trypanosoma cruzi.5,11,15-21 Although some microbial organisms have developed mecha- nisms that may decrease their sensitivity to NO concentrations that are released physiologically, available evidence supports that the high concentrations of NO produced after exogenous application circumvent antimicrobial resistance to NO.5,11,15,16,22-25Cytoprotective Properties NO has also been reported to provide certain cytoprotective properties. These include the following: (1) production of ery- thema in response to ultraviolet (UV) exposure with protection against endothelial cell apoptosis; (2) melanogenesis second- ary to tyrosinase stimulation in response to UV light exposure, which serves to mitigate UV-induced cellular injury; and (3) a relative inhibition of host (mammalian) cell cytotoxicity and lipid peroxidation caused by oxidative injury.5,6,11-13Immunomodulatory Properties In addition to the antimicrobial properties described above, NO has been associated with immunomodulatory activities that can serve to maintain homeostasis within host tissues and in some cases can provide anti-in ammatory effects and tis- sue restorative properties that can mitigate pathophysiologic processes.4,11,15,17,19 Both NO and RNMs can regulate immune response through stimulation of genes that can encode for sev- eral transcription factors and regulatory molecules. Examples of immunodulatory effects of NO include regulation of NF-kB and IL-1β activity, inhibition of in ammasome activity, modulation of T-lymphocyte functions, and effects on matrix metalloproteinase enzymes (MMPs), all of which appear to play a role in acne patho- physiology; and modulation of anti-in ammatory cytokines and possibly MMPs involved in wound healing and tissue repair.4,26-37 The interactions of the several immunomodulatory processes that involve NO and its derivative molecules are summarized in detail elsewhere.4 Suf ce it is to say that speci c biologic proper- ties of NO, if captured in the correct delivery platform, have the potential to provide important therapeutic applications in derma- tology for cutaneous infections, in ammatory dermatoses (ie, acne), and tissue repair/wound healing.2,3,5,11,14,15 Table 2 depicts some of the immunomodulatory effects associated with NO and its derivative molecules, emphasizing those that may have ap- plications in dermatology. What Nitric Oxide-Releasing Delivery Platforms Have Been Evaluated to Date? As noted above, the physiochemical properties of NO that con- found storage stability, and its variable pharmacologic profile based on the concentration released and the duration of target site exposure, provide major challenges in the development
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