Induction of epidermal hyperproliferation by topical n-3 polyunsaturated fatty acids on guinea pig skin linked to decreased levels of 13-hydroxyoctadecadienoic acid (13-hode).
Reversal of essential fatty acid deficiency (EFA) induced epidermal hyperproliferation was recently suggested to require linoleic acid and an active lipoxygenase product. Because the nature of this lipoxygenase product is unknown, we employed a model of n-3 polyunsaturated fatty acid (PUFA) induced hyperproliferation in guinea pig skin to test a possible reversal of the hyperproliferation by an oxidative metabolite of linoleic acid. Topical applications of two n-3 PUFA: 0.5% of eicosapentaenoic acid (20:5n-3) and/or of docosahexaenoic acid (22:6n-3) for 5 d induced severe epidermal hyperproliferation. Development of the epidermal hyperproliferation paralleled a marked decrease in the major epidermal linoleic acid lipoxygenase product (13-hydroxyoctadecadienoic acid; 13-HODE). The application of 0.1% of 13-HODE to the n-3 PUFA-induced guinea pig hyperproliferative skin resulted in the restoration of normal epidermal histology and reversal of hyperproliferation as determined by epidermal uptake of 3H-thymidine. These data support the view that 13-HODE may represent the endogenous cutaneous mediator necessary for full restoration of cutaneous symptoms of essential fatty acid deficiency. Furthermore, the topical use of n-3 PUFA for the disruption of normal metabolism of skin n-6 EFA (linoleic acid) does serve as a useful tool for further investigations into the regulatory mechanisms of in vivo epidermal proliferation/differentiation.
Miller
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Department of Dermatology, School of Medicine, University of California, Davis 95616.
Ziboh
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D000287:Administration, Topical; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006168:Guinea Pigs; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D001095:Arachidonic Acids; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D016718:Arachidonic Acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D004247:DNA; D019787:Linoleic Acid