title: Topically applied manganese-porphyrins BMX-001 and BMX-010 display a significant anti-inflammatory response in a mouse model of allergic dermatitis.
abstract: In this study, we topically administered two antioxidant compounds, the manganese-porphyrin-derivatives BMX-001 and BMX-010, in a mouse model of allergic dermatitis and compared the efficacy for reduction of itch and inflammation. In vitro effects of BMX-001 and BMX-010 on keratinocytes, bone marrow derived dendritic cells (BMDCs) and T-cells were initially analysed. For assessment of scratching behaviour, BMX-001 and BMX-010 (0.01 and 0.1 %) were topically applied 16 h and/or 1 h before compound 48/80 or toluene-2,4,-diisocyanate (TDI) challenge in a TDI induced mouse dermatitis model. Additionally, assessment of allergic skin inflammation was performed in a similar manner in the TDI model. Post-treatment ear thickness was measured 24 h after TDI challenge and compared to basal values. The mice were sacrificed and the ear auricle was removed for further analysis. In vitro, both BMX substances significantly inhibited cytokine production of keratinocytes as well as of BMDC and T-cell proliferation. Topical treatment with BMX cream resulted in a significant decrease in scratching behaviour in the compound 48/80 model, but not in the TDI model. Mice treated with BMX-001 and BMX-010 showed a moderate dose dependent decrease in ear thickness, and interestingly, the concentration of the cytokines IL-1β and IL-4 in inflamed skin was reduced by 80-90 % by all treatment options. These first results suggest the potential benefit of a BMX-001 and BMX-010 cream for the treatment of allergic-inflammatory skin diseases.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Stover
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fukuyama
authors.affiliation: Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina, Chapel Hill, Chapel Hill, USA.
authors.forename: Ashlyn T
authors.initials: AT
authors.lastname: Young
authors.affiliation: Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina, Chapel Hill, Chapel Hill, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Daniele
authors.affiliation: BioMimetix JV, LLC, Englewood, CO, USA.|University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Oberley
authors.affiliation: BioMimetix JV, LLC, Englewood, CO, USA.|National Jewish Health, Denver, CO, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA. wolfgang_baeumer@ncsu.edu.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bäumer
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy*; D004195:Disease Models, Animal; D004423:Ear; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D011537:Pruritus / Q000188:drug therapy*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D063465:Skin Cream; D013482:Superoxide Dismutase / Q000378:metabolism; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D008665:Metalloporphyrins; C521294:Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin; C520506:manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin; D014051:Toluene 2,4-Diisocyanate; D015847:Interleukin-4; D003189:p-Methoxy-N-methylphenethylamine; D013482:Superoxide Dismutase
keywords: Allergic dermatitis; BMX-001; BMX-010; Mice; Superoxide dismutase mimics