Steroid-induced atrophy in an animal and human model

Abstract

A ratchet-controlled micrometer screw gauge has been used to measure the changes in skin thickness produced by topical corticosteroids. Measurable thinning of the mouse ear followed repeated daily application of corticosteroids. This response in the animal was used to assess the atrophic potential in a variety of standard formulations. The same compounds were applied to human skin and the changes in thickness measured. Patterns of response and the rank order of thinning obtained from the animal model were found to parallel closely the human results.

Adverse effects of topical glucocorticosteroids

“…Other test systems include the ammonium hydroxide blister tests, 25 the stratum corneum test, 24 the skin thickness measurement, 26 the acne induction test, 27 and the assessment of endogenous cortisol production. 21,28,29 The psoriasis plaque test, the poison ivy test, and the contact eczema inhibition test are only of historic value.…”

Test systems for the determination of glucocorticoid receptor ligand induced skin atrophy

“…19 Atrophogenicity has been evaluated in mice, 32,33 in rats, 34,35 in pigs 36,37 and in dogs. 3 Castor and Baker showed as early as 1950 that topical application of hydrocortisone to rat skin caused dermal thinning.…”

“…38 Overall the rat seems to be the best suited species. In the past, rats were shaved for atrophy assessment; 32,39 however, due to the unreliability of haired skin responses, 40,41 the use of hairless animals is the preferred now. Indeed, the current gold standard for pre-clinical testing of GR ligands is the hairless OFA hr/hr rat.…”

“…29,30 It has been shown, that the following parameters of GC-induced skin atrophy can be detected human skin such as the high number of skin appendages and the absence of a papillary dermis in rodents clearly might influence pharmacokinetics. 32 Therefore, absorption of topically administered compounds in rodent skin can exceed human skin by ten times.…”

Treatment of Skin Inflammation with Benzoxaborole Phosphodiesterase Inhibitors: Selectivity, Cellular Activity, and Effect on Cytokines Associated with Skin Inflammation and Skin Architecture Changes

“…The effect of each compound on mouse skin thickness was evaluated using hairless SKH-1 mice (eight mice per group) generally following the protocol of Kirby and Munro (1976), with the addition of histopathology as reviewed by Schoepe et al (2006). The baseline thickness of the dorsal skin was measured using calipers prior to drug treatment.…”