T Fukuyama1, B C Martel1, K E Linder2, S Ehling1, J R Ganchingco1, W Bäumer1,3. 1. Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. 2. Department of Population Health and Pathology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. 3. Department of Veterinary Medicine, Institute of Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany.
Abstract
BACKGROUND: It has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis; however, the specific antipruritic mechanism of action remains unclear. OBJECTIVE: To confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl's mode of action. METHODS: In this study, the effects of topical administration of HOCl hydrogel (0.05%) on atopic dermatitis-like lesions in NC/Nga mice model as well as in vitro effects of HOCl on dorsal root ganglia neurons and mouse bone marrow-derived dendritic cells (mBMDCs) were investigated. NC/Nga mice were sensitized with house dust mite allergen and treated topically with HOCl hydrogel both preventively and therapeutically against established lesions. Allergen challenge was continued during HOCl hydrogel application. RESULTS: Treatment with HOCl hydrogel prevented the development of lesions and scratching bouts during the whole observation period. When administered after full development of lesions, HOCl reduced lesions and scratching behaviour to a similar extent as a positive control 0.1% betamethasone dipropionate ointment. The reduced inflammatory response by HOCl treatment was demonstrated by reduced secretion of inflammatory cytokines in affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL-12 production in mBMDC. The diminished scratching behaviour was confirmed by impaired response to several pruritogens in dorsal root ganglia neurons excised from NC/Nga mice after termination of the studies. The response to the stimuli was also reduced by pre-incubation of sensory neurons from untreated BALB/c mice with 0.0001% HOCl. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate a direct reduction in sensory response by HOCl, leading to significantly reduced itch and inflammation in vivo.
BACKGROUND: It has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in humanpatients with atopic dermatitis; however, the specific antipruritic mechanism of action remains unclear. OBJECTIVE: To confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl's mode of action. METHODS: In this study, the effects of topical administration of HOCl hydrogel (0.05%) on atopic dermatitis-like lesions in NC/Nga mice model as well as in vitro effects of HOCl on dorsal root ganglia neurons and mouse bone marrow-derived dendritic cells (mBMDCs) were investigated. NC/Nga mice were sensitized with house dust mite allergen and treated topically with HOCl hydrogel both preventively and therapeutically against established lesions. Allergen challenge was continued during HOCl hydrogel application. RESULTS: Treatment with HOCl hydrogel prevented the development of lesions and scratching bouts during the whole observation period. When administered after full development of lesions, HOCl reduced lesions and scratching behaviour to a similar extent as a positive control 0.1% betamethasone dipropionate ointment. The reduced inflammatory response by HOCl treatment was demonstrated by reduced secretion of inflammatory cytokines in affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL-12 production in mBMDC. The diminished scratching behaviour was confirmed by impaired response to several pruritogens in dorsal root ganglia neurons excised from NC/Nga mice after termination of the studies. The response to the stimuli was also reduced by pre-incubation of sensory neurons from untreated BALB/c mice with 0.0001% HOCl. CONCLUSIONS AND CLINICAL RELEVANCE: These data indicate a direct reduction in sensory response by HOCl, leading to significantly reduced itch and inflammation in vivo.
Authors: Sara Majewski; Tanya Bhattacharya; Manuela Asztalos; Benjamin Bohaty; Katherine C Durham; Dennis P West; Adelaide A Hebert; Amy S Paller Journal: Pediatr Dermatol Date: 2019-04-15 Impact factor: 1.588
Authors: Lori I Robins; Erika K Keim; Deborah B Robins; John S Edgar; John S Meschke; Philip R Gafken; Jeffrey F Williams Journal: ACS Omega Date: 2021-12-14