Separation of retinoid-induced epidermal and dermal thickening from skin irritation.
The ability of the synthetic retinoid MDI-301, in which the carboxylic acid of 9- cis-retinoic acid (9-cis-RA) is replaced with an ester linkage, to induce epidermal and dermal thickening and skin irritation (erythema and flaking) in hairless (rhino) mice following its topical application was investigated in comparison with that of 14-all- trans-retinoic acid (14-all-trans-RA) and 9-cis-RA. MDI-301 induced epidermal proliferation leading to a thickened epidermis. Treated animals also demonstrated a prominent band of organized connective tissue immediately below the epidermis. In its ability to induce epidermal thickening, MDI-301 was quantitatively similar to 14-all-trans-RA and 9-cis-RA. However, unlike 14-all-trans-RA and 9-cis-RA, which produced skin irritation associated with a perivascular influx of mononuclear leukocytes into the dermis, there was no evidence of irritation with MDI-301 and little leukocyte infiltration. Intraperitoneal injection of either 14-all-trans-RA or MDI-301 also resulted in epidermal and dermal thickening. Irritation of skin was not observed in these animals but splenomegaly was prominent in animals treated with either agent.
Varani
James
J
Department of Pathology, The University of Michigan, 1301 Catherine Road, Box 0602, Ann Arbor, MI 48109, USA. varani@umich.edu
Fligiel
Helene
H
Zhang
Jian
J
Aslam
Muhammad Nadeem
MN
Lu
Yi
Y
Dehne
Lindsay A
LA
Keller
Evan T
ET
D000077556:Alitretinoin; D000818:Animals; D002478:Cells, Cultured; D017453:Dermatitis, Irritant / Q000473:pathology*; D020405:Dermis / Q000473:pathology*; D004817:Epidermis / Q000473:pathology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008812:Mice, Hairless; D012176:Retinoids / Q000737:chemistry / Q000494:pharmacology*; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
C488463:MDI 301; D012176:Retinoids; D000077556:Alitretinoin; D014212:Tretinoin