Chronic ethanol ingestion alters xenobiotic absorption through the skin: potential role of oxidative stress.

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.

Potential mechanisms by which a single drink of alcohol can increase transdermal absorption of topically applied chemicals.

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.

Moisturizing lotions can increase transdermal absorption of the herbicide 2,4-dichlorophenoxacetic acid across hairless mouse skin.

Moisturizing lotions can be an effective treatment for occupationally induced dry skin. These compounds are designed to be hygroscopic and retain water to keep the stratum corneum hydrated, while at the same time enhancing the horny layer to prevent increases in transepidermal water loss (TEWL). Skin hydration levels, however, are known to influence barrier properties. The purpose of this work was to compare skin moisture levels induced by four commercially available moisturizing lotions with their capacity as transdermal penetration enhancers using the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) as a model chemical. Further, the effect of moisturizing the skin after washing with sodium lauryl sulfate (SLS) on transdermal absorption was determined. Skin moisture levels were also measured noninvasively and were correlated to penetration enhancement. Hairless mouse skin was pretreated with commercially available moisturizing lotions either with or without SLS washing and in vitro permeability studies were performed with the herbicide 2,4-D. The data demonstrate that pretreatment with three of the four lotions tested increased the transdermal absorption of 2,4-D as evidenced by cumulative penetration or faster lag times (p < 0.05). Skin moisture levels correlated with the penetration enhancement capabilities of the lotion. Washing the skin with 5% SDS increased the transdermal absorption of 2,4-D (p < 0.05) and application of moisturizing lotions increased the absorption further. In summary moisturizing lotions may influence transdermal penetration of the skin, with the more effective moisturizers having a greater effect on 2,4-D absorption.

Transdermal absorption of the herbicide 2,4-dichlorophenoxyacetic acid is enhanced by both ethanol consumption and sunscreen application.

Xenobiotics absorption is a health concern and skin is a major exposure site for many of these chemicals. Both alcohol consumption and topical sunscreen application act as transdermal penetration enhancers for model xenobiotics. The effect of combining these two treatments on transdermal absorption of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was therefore examined. Skin from rats ingesting low (1.5 g/kg) medium (4.3 g/kg) or high (6 g/kg) ethanol doses or saline control was treated with a commercially available sunscreen containing titanium dioxide and octyl methoxycinnimate and transdermal absorption of 2,4-D was monitored. Ethanol increased penetration by a factor of 1.9, 2.0 and 2.5 for animals treated with 1.5, 4.3 and 6 g/kg respectively, demonstrating an ethanol-induced dose response. Sunscreen application to skin from ethanol gavaged rats caused 2,4-D absorption above that induced by ethanol alone by an additional factor of 1.3, 2.1 and 2.9 for 1.5, 4.3 and 6 g/kg respectively. Comparing 2,4-D transdermal absorption after exposure to both ethanol and sunscreen with a theoretical value (sum of penetration after ethanol or sunscreen treatment) demonstrates that these two treatments enhance additively at the higher doses tested. Results of this study emphasize the importance of limiting excessive alcohol consumption in individuals with potential herbicide exposure rather than discouraging the use of sunscreens, since the consequences of UV-induced skin cancer are far more series than the risks that would be associated with observed increases in chemical exposure.