title: Chronic ethanol ingestion alters xenobiotic absorption through the skin: potential role of oxidative stress.
abstract: Alcohol ingestion is correlated with several skin disorders and it has been proposed that changes in skin properties may be an early indicator of alcohol misuse. Topically applied ethanol is an effective transdermal penetration enhancer; however, little is known about the effects of chronic ethanol ingestion on skin. Rats were pair fed a diet containing 36% ethanol for twelve weeks. The animals were then switched to a non-ethanol diet and were monitored for up to four weeks. Non-invasive measurements for changes in dermal blood flow using laser Doppler velocimetry (LDV), damage to skin barrier via transepidermal water loss (TEWL) and changes in skin moisture content were obtained for the experimental duration. At 0, 1 day or 1, 2, 3, 4 weeks after alcohol removal rats were euthanized and their skin was analyzed for alcohol and aldehyde dehydrogenase, and lipid peroxidation. Transdermal penetration of the herbicide paraquat, industrial solvent dimethyl formamide (DMF), insect repellant N,N-diethyl-m-toluamide (DEET) and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was also determined. Transdermal absorption, LDV, TEWL, skin alcohol and aldehyde dehydrogenase, as well as lipid peroxidation significantly increased after continuous ethanol exposure (p<0.05). These factors remain elevated for up to four weeks after termination of ethanol consumption, showing that skin changes induced by alcohol are not immediately reversible and reflect fundamental changes in the skin itself. This work provides a starting point for examining the link between ethanol ingestion and skin disorders associated with alcohol use.
authors.affiliation: Departments of Dermatology and Medicine, University of Pittsburgh Medical Center, 190 Lothrop Street, 145 Lothrop Hall, Pittsburgh, PA 15213, United States. brandr@dom.pitt.edu
authors.forename: R M
authors.initials: RM
authors.lastname: Brand
authors.forename: J L
authors.initials: JL
authors.lastname: Jendrzejewski
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000493:pharmacokinetics; D000426:Alcohol Dehydrogenase / Q000032:analysis; D000444:Aldehyde Dehydrogenase / Q000032:analysis; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003671:DEET / Q000493:pharmacokinetics; D004058:Diffusion; D004126:Dimethylformamide / Q000493:pharmacokinetics; D000431:Ethanol / Q000494:pharmacology*; D006540:Herbicides / Q000493:pharmacokinetics; D007302:Insect Repellents / Q000493:pharmacokinetics; D017078:Laser-Doppler Flowmetry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010269:Paraquat / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D012869:Skin Absorption / Q000187:drug effects*; D014870:Water Loss, Insensible / Q000187:drug effects; D015262:Xenobiotics / Q000493:pharmacokinetics*
chemical_list: D002492:Central Nervous System Depressants; D006540:Herbicides; D007302:Insect Repellents; D015262:Xenobiotics; D003671:DEET; D015084:2,4-Dichlorophenoxyacetic Acid; D000431:Ethanol; D008315:Malondialdehyde; D004126:Dimethylformamide; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D010269:Paraquat