Animal assays for anti-psoriatic., retinoid and sunprotective agents

Abstract

It is possible to evaluate different dermatological therapeutic agents intended for human use in a variety of animal assays. This review will discuss some of these assays, and attempt to correlate animal and human skin responses. Psoriasis is a disease where changes in epidermal proliferation may be an important factor. It is possible to assay potential anti-psoriatic agents by measuring their ability to suppress DNA synthesis in the epidermis of hairless mice. This assay is predictive of the anti-psoriatic effectiveness of numerous agents including a variety of anti-proliferative drugs and anthralin, and has been used to evaluate the potential efficacy of purified coal tar shampoos and body preparations. The activity of the polyamine biosynthesis enzyme ornithine decarboxylase (ODC) is elevated in psoriatic skin, and it is induced in mouse epidermis by tape stripping. Retinoids can inhibit the induction of ODC activity, and this inhibition may be used to evaluate novel synthetic retinoids. Retinoids have beneficial effects on the abnormal keratinization found in various diseases. Rhino mice have multiple keratin-filled epidermal utricles, and the size of these is reduced by retinoid treatment. Observing the changes in the size of the utricles can be utilized to evaluate the effects of retinoids on keratinization. Sunscreen agents are tested on human volunteers by observing their ability to inhibit the erythema induced by exposure to solar-simulated light, to obtain a sun protection factor (SPF). It is possible to utilize the ability of sunscreens to inhibit other actinic-induced changes in the skin using animals. Parameters that may be measured include changes in DNA synthesis and ODC activity in the epidermis following ultraviolet irradiation. Some of these assays correlate well with human SPF determinations.

Shedding light on sunscreens

“…In all of these methods, a standard reference formulation is tested alongside the sunscreen to serve as a control; this contains homomenthyl salicylate in the FDA and SAA methods, 63 2‐ethylhexyl p ‐methoxycinnamate in the DIN method, 63 and the choice of three reference formulations in the Colipa method. In addition to these well recognized methodologies, several other in vivo methods using human 64 , 65 or animal 66 –76 skin have been suggested but not become widely used.…”

The mouse epidermis as a model in skin pharmacology: influence of age and sex on epidermal metabolic reactions and their circadian rhythms

“…Drugs for topical or systemic treatment of skin diseases are tested in vitro using keratinocyte cultures or in vivo in human beings or in laboratory animals (Wrench, 1981;Marks et al, 1983;Zmolek et al, 1983;Lowe et al, 1984;van den Hoven et al, 1987;Hofbauer et al, 1988;Lubach & Kietzmann, 1988a,b;Kietzmann & Lubach, 1989). Because of differences in the histology and metabolism of the epidermis of different skin regions, the compatibility of results is often poor.…”