title: The antiwrinkle effect of topical concentrated 2-dimethylaminoethanol involves a vacuolar cytopathology.
abstract: BACKGROUND
  The 'cosmeceutical' agent 2-dimethylaminoethanol (DMAE) is a tertiary amine found in high concentration in numerous topical antiwrinkle preparations.
  
  
  OBJECTIVE
  We hypothesized that a 337 mmol L(-1) (3%) DMAE reservoir applied to the skin could reproduce the cytopathology induced by other amines by maintaining a millimolar drug concentration within a certain depth of the skin layers, and that vacuolar cell expansion could account for the very rapid effect on the apparent skin fullness.
  
  
  METHODS
  Morphological and functional assays were applied to cultured rabbit dermal fibroblasts treated with tertiary amines in vitro. A morphological verification of the vacuolization caused by topical DMAE was also attempted in vivo using the inner skin of the rabbit ear and in vitro using primary cultures of human cutaneous epithelial cells.
  
  
  RESULTS
  Fibroblasts responded to DMAE (2.5-10 mmol L(-1)) by massive vacuolization (0.5-4 h; phase contrast observations). Triethanolamine, another chemical frequently used topically, was also active in this respect (10 mmol L(-1)). The vacuolar adenosine triphosphatase inhibitor bafilomycin A1 prevented DMAE- or triethanolamine-induced vacuolization; adding bafilomycin A1 or cell washout slowly reversed the established vacuolization induced by DMAE. Further effects of DMAE in cultured fibroblasts included a moderate cytotoxicity (10 mmol L(-1)) that was abated by bafilomycin A1 cotreatment, a concentration-dependent mitotic arrest (2.5 mmol L(-1)) and transient and mild effects on cell ploidy. The epidermis of the rabbit external ear was significantly thickened and exhibited clear perinuclear swelling indicative of vacuolization in response to 3% DMAE (1 h; paraffin tissue sections). Cultured human cutaneous epithelial cells responded to DMAE by vacuolization (inhibited by bafilomycin A1 cotreatment).
  
  
  CONCLUSIONS
  The vacuolar cytopathology induced by concentrated organic amines may be the cellular basis of the antiwrinkle effect of DMAE.
authors.affiliation: Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Québec QC, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Morissette
authors.forename: L
authors.initials: L
authors.lastname: Germain
authors.forename: F
authors.initials: F
authors.lastname: Marceau
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003358:Cosmetics / Q000494:pharmacology; D003642:Deanol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008858:Microscopy, Phase-Contrast; D011817:Rabbits; D012867:Skin / Q000166:cytology / Q000187:drug effects*; D015595:Skin Aging / Q000187:drug effects*; D014617:Vacuoles / Q000187:drug effects*
chemical_list: D003358:Cosmetics; D003642:Deanol