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- Original article -
Pharmacological Profiles of High-Concentration (20 µg/g) Tacalcitol Ointment: Effects on Cutaneous Inflammation, Epidermal Proliferation, and Differentiation in Mice
Hiroaki Sato, Yasuhiro Ogino, Hideko Takagi, Junko Hata*, Satoshi Asano*, Tomohiro Ohta and Keiji Komoriya
Pharmacological Research Department, Pharmaceuticals Development Research Laboratories, Teijin Institute for Bio-Medical Research, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan.
*Safety Research Department, Pharmaceuticals Development Research Laboratories, Teijin Institute for Bio-Medical Research, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan.
This study focused on the effects of tacalcitol (1,24 (R) (OH)2D3, TV-02) ointment
(20 µg/g) on cutaneous inflammation, epidermal proliferation, and differentiation and compared them with tacalcitol ointment (2 µg/g) and other anti-psoriatic ointments using hairless mice. Tacalcitol ointment (0, 2 and 20 µg/g) significantly inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cutaneous inflammation, histopathologically. The effect of tacalcitol ointment (20 µg/g) on cutaneous inflammation was much stronger than that of tacalcitol ointment (0, 2 µg/g), and as effective as calcipotriol ointment (50 µg/g) or betamethasone valerate ointment (1.2 mg/g). Tacalcitol ointment (20 µg/g) also significantly inhibited TPA-induced myeloperoxidase (MPO) activity, as effectively as calcipotriol ointment (50 µg/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 µg/g to 20 µg/g. The effect of tacalcitol ointments on epidermal proliferation was significant at the doses of 2 µg/g and 20 µg/g, and that on epidermal differentiation was significant at the doses of 0.2 µg/g or more. The effect of tacalcitol ointment (20 µg/g) on epidermal differentiation was significantly stronger than tacalcitol ointment (2 µg/g). In this study, tacalcitol ointment (20 µg/g) was found to have a marked effect on cutaneous inflammation and improved effect on epidermal differentiation, although tacalcitol ointment (2 µg/g) also had significant effects on epidermal proliferation and differentiation. These findings support the clinical effectiveness of tacalcitol ointment (20 µg/g) against psoriasis.
key words: tacalcitol; psoriasis; inflammation; proliferation; differentiation
Received January 6, 2003; Accepted for publication April 30, 2003
Reprint requests to: Hiroaki Sato, Pharmacological Research Department, Pharmaceuticals Development Research Laboratories, Teijin Institute for Bio-Medical Research, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan.
J Dermatol 30 (7): 510-524, 2003
Japanese Dermatological Association
http://www.dermatol.or.jp
