title: Pharmacological profiles of high-concentration (20 microg/g) tacalcitol ointment: effects on cutaneous inflammation, epidermal proliferation, and differentiation in mice.
abstract: This study focused on the effects of tacalcitol (1,24 (R) (OH)2D3, TV-02) ointment (20 micro g/g) on cutaneous inflammation, epidermal proliferation, and differentiation and compared them with tacalcitol ointment (2 micro g/g) and other anti-psoriatic ointments using hairless mice. Tacalcitol ointment (0, 2 and 20 micro g/g) significantly inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cutaneous inflammation, histopathologically. The effect of tacalcitol ointment (20 micro g/g) on cutaneous inflammation was much stronger than that of tacalcitol ointment (0, 2 micro g/g), and as effective as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). Tacalcitol ointment (20 micro g/g) also significantly inhibited TPA-induced myeloperoxidase (MPO) activity, as effectively as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). The effect of tacalcitol ointment on epidermal proliferation [ornithine decarboxylase (ODC) activity] and differentiation [transglutaminase (TGase) activity] was dose-dependent from 0 micro g/g to 20 micro g/g. The effect of tacalcitol ointments on epidermal proliferation was significant at the doses of 2 micro g/g and 20 micro g/g, and that on epidermal differentiation was significant at the doses of 0.2 micro g/g or more. The effect of tacalcitol ointment (20 micro g/g) on epidermal differentiation was significantly stronger than tacalcitol ointment (2 micro g/g). In this study, tacalcitol ointment (20 micro g/g) was found to have a marked effect on cutaneous inflammation and improved effect on epidermal differentiation, although tacalcitol ointment (2 micro g/g) also had significant effects on epidermal proliferation and differentiation. These findings support the clinical effectiveness of tacalcitol ointment (20 micro g/g) against psoriasis.
authors.affiliation: Pharmacological Research Department, Pharmaceuticals Development Research Laboratories, Teijin Institute for Bio-Medical Research, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sato
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogino
authors.forename: Hideko
authors.initials: H
authors.lastname: Takagi
authors.forename: Junko
authors.initials: J
authors.lastname: Hata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asano
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ohta
authors.forename: Keiji
authors.initials: K
authors.lastname: Komoriya
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001707:Biopsy, Needle; D003872:Dermatitis / Q000188:drug therapy* / Q000473:pathology*; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008812:Mice, Hairless; D009824:Ointments; D011565:Psoriasis / Q000188:drug therapy / Q000473:pathology; D012016:Reference Values; D016896:Treatment Outcome
chemical_list: D004100:Dihydroxycholecalciferols; D009824:Ointments; C023850:1 alpha,24-dihydroxyvitamin D3