Tazarotene Induces Epidermal Cell Differentiation in the Mouse Tail Test Used as an Animal Model for Psoriasis

Abstract

Disturbed epidermal proliferation and keratinization are major features of psoriatic skin lesions. The so-called mouse tail test is known as an animal model to evaluate the antipsoriatic efficacy of topical drugs with rgard to the induction of orthokeratosis. The purpose of the present study was to investigate the effect of tazarotene, a novel, receptor-specific retinoid, by the mouse tail test in a direct comparison to dithranol representing a classical topical antipsoriatic compound. The tails of CFLP mice were treated with tazarotene gel (0.1%, 0.05%), dithranol ointment (1.0%), tretinoin cream (0.05%) and methylcellulose (5%) hydrogel (vehicle control) for 2 weeks. Longitudinal histological sections were prepared from the tail skin, and the degree of orthokeratosis was determined by measuring the horizontal length of the fully developed granular layer within an individual scale in relation to its total length according to a method originally described by Bosman and co-authors. The degree of orthokeratosis was significantly (p ≤ 0.05) increased by 0.1% tazarotene (87 ± 20%), 1.0% dithranol (75 ± 26%), 0.05% tazarotene (59 ± 27%), and 0.05% tretinoin (23 ± 13%) as compared to untreated (11 ± 6%) and methylcellulose hydrogel-treated (13 ± 6%) controls. Under the conditions of the mouse tail test, tazarotene showed a strong potency to induce orthokeratosis. With regard to clinically relevant concentrations this effect was even more pronounced than that observed for dithranol.

Screening of Caesalpinia bonduc leaves for antipsoriatic activity

“…On the other hand, CBD, CBDB and CBHA showed significant change in epidermal thickness but did not produce significant orthokeratosis. In our study, we did not find any correlation between the percentage relative epidermal thickness and percentage orthokeratosis and this is in contradiction with Sebok et al (2000). Representative examples of the histological specimens underlying the histometrical investigation are shown in Fig.…”

“…Induction of orthokeratosis in the adult mousetail is the basis behind the mouse tail test (Vogel, 2008). Many drugs presently used in the treatment of psoriasis have been evaluated by the mouse tail test and were found to have shown good efficacies (Sebok et al, 2000). Hence in the present study, we used the mouse tail test for evaluating the efficacy of Caesalpinia bonduc extracts and fractions.…”

Ethyl acetate fraction of Radix rubiae inhibits cell growth and promotes terminal differentiation in cultured human keratinocytes

“…Calcipotriol, a Vitamin D3 analog for psoriasis, is able to induce differentiation in human keratinocytes (Takahashi et al, 2003). Tazarotene, a retinoid for psoriasis, is capable of downregulating keratinocyte differentiation markers TG1 and K16 in psoriasis through direct action on keratinocyte gene expression (Nagpal et al, 1996;Sebok et al, 2000). Many effective tropical therapeutic agents for psoriasis, applied either as monotherapy or combination with UVB therapy, were shown to inhibit keratinocyte proliferation and induce epidermal differentiation in psoriatic skin (Van der Vleuten et al, 1996).…”

Enhancement of the Antiparakeratotic Potency of Calcitriol and Tacalcitol in Liposomal Preparations in the Mouse Tail Test

“…By measuring the ability of topically applied medications to transform the partial parakeratosis normally present in the mouse epidermis to orthokeratosis, this test has been used to investigate the antiparakeratotic potency of various antipsoriatic drugs, such as dithranol, retinoic acid, tar [12,14], lipoxygenase and cyclooxygenase inhibitors [15], fumaric acid esters, betamethasone, calcipotriol [16], and tazarotene [17].…”