Testing of Lipoxygenase Inhibitors, Cyclooxygenase Inhibitors, Drugs with Immunomodulating Properties and Some Reference Antipsoriatic Drugs in the Modified Mouse Tail Test, an Animal Model of Psoriasis

Abstract

Topical administration of lipoxygenase and cyclooxygenase inhibitors, antipsoriatic drugs and some immunomodulating drugs on adult mouse tail scales showed variable induction of of orthokeratosis. Dithranol and retinoic acid showed ED₅₀ concentrations of 0.5% and 0.23%, respectively. The lipoxygenase inhibitors catechol and octyl gallate showed ED₅₀ of 2.5 and 13.4%. 10% lonapalene showed 20% activity, curcumin, linoleic acid, primrose oil and AA673 10–15% activity, methyl and ethyl gallate 5% activity, nordihydroguaiaretic acid, diethylcarbamazine, ebselen, esculetin, quercetin, AA861, gallic acid, dodecyl gallate and 15-hydroxyeicosatetraenoic acid no activity. The cyclooxygenase inhibitors indomethacin, acetylsalicylic acid and bufexamac were inactive, benoxaprof-en showed 14% activity. The immunomodulating drugs fluo-rouracil and triamcinolone showed > 10% activity, cyclosporin A and thalidomide no activity. Fumaric acid showed 5% activity. The results show that this model could be proposed for screening antipsoriatic drugs.

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

“…In the present study we observed for tazarotene (0.1%) a potency to restore orthokeratosis and orthogranulosis which was more pronounced than that found with dithranol (1.0%). This high efficacy of tazarotene to induce epidermal differentiation in vivo is underlined when considering literature data on a variety of antipsoriatics tested in the modified mouse tail test [11,12,14]. A degree of orthokeratosis of 87% as observed for 0.1% tazarotene in the present study is not exceeded by any antipsoriatic studied earlier as shown in table 3.…”

“…The mouse tail test first described by Jarrett and Spearman [10], with certain modifications reported by others [11,12], is a morphometry-based, relatively sensitive and well reproducible method which allows the quantitative evaluation of the effects of antipsoriatic drugs on epidermal differentiation [13,14], crucially disturbed in psoriasis.…”

Curcumin: an orally bioavailable blocker of TNF and other pro‐inflammatory biomarkers

“…This observed phototoxicity makes curcumin a potential photosensitizing drug, which could be used in phototherapy of psoriasis. Secondly, when curcumin was tested as an anti-psoriatic drug in the modified mouse tail test, an animal model of psoriasis, it exhibited some activity (Bosman, 1994). Thirdly, curcumin has been shown to inhibit the proliferation of human keratinocytes through suppression of pro-inflammatory pathways (Pol et al, 2003;Cho et al, 2007).…”

Effect of Fumaric Acid, Its Dimethylester, and Topical Antipsoriatic Drugs on Epidermal Differentiation in the Mouse Tail Model

“…The mouse tail test first described by Jarrett and Spearman [9] in 1964, with certain modifications recently reported by others [10,11], is a relatively sensitive method [ 12] which allows the quantitative evaluation of the effects of antipsoriatic agents on cell dif ferentiation. In previous studies in vitro we demonstrated that of the fumaric acid deriva tives, the fumaric acid dimethylester and of the dithranol compounds, C4-lactone were the most effective on kératinocyte prolifera tion at subtoxic concentrations [13,14], Therefore, in the present study we compare the effects of fumaric acid, fumaric acid di methylester, and C4-lactone with that of clas sic topical antipsoriatics on kératinocyte mat uration in vivo.…”