title: Potential mechanisms by which a single drink of alcohol can increase transdermal absorption of topically applied chemicals.
abstract: BACKGROUND
  Both chronic and acute ethanol consumption increase transdermal penetration of topically applied xenobiotics. The mechanisms by which this enhancement occurs are unknown. We hypothesized that either the vasodilatory effects of ethanol or its ability to disrupt the lipid bilayer via lipid peroxidation, may be contributing to the increased transdermal absorption observed in alcohol consuming animals.
  
  
  METHODS
  Male Wistar rats were gavaged with 1.5, 3, 4.3, 6 or 10 g/kg ethanol or saline control or were treated with either the vasoconstrictor epinephrine or with the vasodilator prilocaine. Dermal blood flow, transepidermal water loss (TEWL), and skin moisture were non-invasively measured. Transdermal penetration was then determined for four xenobiotics (paraquat, dimethyl formamide (DMF), 2,4-dichlorophenoxyacetic acid (2,4-D) and N,N-diethyl-m-toluamide (DEET)). Lipid peroxidation was also determined by monitoring the formation of malondialdehyde.
  
  
  RESULTS
  Dermal blood flow increased by approximately 27% (p<0.05), TEWL increased 1.12+/-0.2-fold while skin lipid peroxidation increased 1.4-fold (p<0.05) 2h after gavage with 10 g/kg alcohol. Transdermal penetration of paraquat was increased by prilocaine (ER=2.1+/-0.4, p<0.05), but the absorption of DEET, 2,4-D and DMF were not influenced by greater blood flow. Reducing dermal blood flow with epinephrine did not cause any significant changes in transdermal penetration.
  
  
  CONCLUSIONS
  Vasodilation triggered by a single episode of ethanol ingestion is not responsible for the observed increase in transdermal absorption. Ethanol induced changes in lipid peroxidation and TEWL demonstrate that drinking alcohol induces transdermal absorption of xenobiotics.
authors.affiliation: Division of Emergency Medicine, Evanston Northwestern Healthcare, Evanston, IL 60201, USA. RHBRAND@ENH.ORG
authors.forename: R M
authors.initials: RM
authors.lastname: Brand
authors.forename: J L
authors.initials: JL
authors.lastname: Jendrzejewski
authors.forename: Anna R
authors.initials: AR
authors.lastname: Charron
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000008:administration & dosage; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D003671:DEET / Q000008:administration & dosage; D004126:Dimethylformamide / Q000008:administration & dosage; D004837:Epinephrine / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage*; D006540:Herbicides / Q000008:administration & dosage; D007302:Insect Repellents / Q000008:administration & dosage; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D010269:Paraquat / Q000008:administration & dosage; D011318:Prilocaine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage; D014867:Water / Q000378:metabolism
chemical_list: D006540:Herbicides; D007302:Insect Repellents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D011318:Prilocaine; D014867:Water; D003671:DEET; D015084:2,4-Dichlorophenoxyacetic Acid; D000431:Ethanol; D008315:Malondialdehyde; D004126:Dimethylformamide; D010269:Paraquat; D004837:Epinephrine