New model of a scaling dermatosis: induction of hyperproliferation in hairless mice with eicosa-5,8,11-trienoic acid.
The present studies have demonstrated that topical application of a low concentration of eicosa-5,8,11-trienoic acid (a 20:3,n9 fatty acid previously reported to inhibit competitively the activity of the sheep vesicular cyclooxygenase) to skin of normal fed hairless mice produced severe scaly dermatosis which is characterized by marked hyperplasia and acanthosis of the epidermal layer. The precise mechanism of this induction of scaly dermatosis is presently unclear. It is nonetheless interesting that the treatment of skin with similar concentrations of other unsaturated fatty acids produced no visible or histologic effects. Furthermore, endogenous levels of arachidonic acid in epidermal phospholipid and triglyceride fractions were shown to increase significantly (p < 0.01) in skin treated with the 20:3,n9 fatty acid while the endogenous level of PGE2 in the same tissue decreased markedly. This latter observation is consistent at least in part, with a previous report from this laboratory in which the 20:3,n9 fatty acid inhibited in vitro the activity of the sheep vesicular cyclooxygenase (the rate limiting enzyme in the transformation of arachidonic acid into the prostaglandin endoperoxides) although the increase in arachidonic acid may also reflect an increased incorporation of this fatty acid into the epidermal lipids by the hyperproliferative tissue. Evaluation of the proliferative status of 20:3,n9 fatty acid-treated skin showed a significant increase (p < 0.01) in labeling and mitotic indices. The use of this potentially endogenous fatty acid may be a useful tool for further investigations of hyperproliferative skin diseases where dietary deficiency of essential fatty acids does not exist.
D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology* / Q000031:analogs & derivatives; D000818:Animals; D001095:Arachidonic Acids / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D008055:Lipids / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D011458:Prostaglandins E / Q000032:analysis; D012867:Skin / Q000032:analysis / Q000187:drug effects* / Q000473:pathology; D012871:Skin Diseases / Q000473:pathology*
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D008055:Lipids; D011458:Prostaglandins E; D015126:8,11,14-Eicosatrienoic Acid; C010944:mead acid