Brand R M, Jendrzejewski J L, Charron Anna R
Division of Emergency Medicine, Evanston Northwestern Healthcare, Evanston, IL 60201, USA.
Toxicology. 2007 Jun 25;235(3):141-9. doi: 10.1016/j.tox.2007.03.008. Epub 2007 Mar 15.
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.
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.
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.
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.
长期和急性乙醇摄入均会增加经皮局部应用的外源性物质的透皮渗透率。这种增强作用发生的机制尚不清楚。我们推测，乙醇的血管舒张作用或其通过脂质过氧化破坏脂质双分子层的能力，可能是导致在饮酒动物中观察到的透皮吸收增加的原因。
给雄性Wistar大鼠灌胃1.5、3、4.3、6或10 g/kg乙醇或生理盐水作为对照，或者用血管收缩剂肾上腺素或血管舒张剂丙胺卡因进行处理。采用非侵入性方法测量皮肤血流量、经表皮水分流失（TEWL）和皮肤水分含量。然后测定四种外源性物质（百草枯、二甲基甲酰胺（DMF）、2,4-二氯苯氧乙酸（2,4-D）和N,N-二乙基间甲苯酰胺（避蚊胺））的透皮渗透率。还通过监测丙二醛的形成来测定脂质过氧化。
灌胃10 g/kg酒精2小时后，皮肤血流量增加约27%（p<0.05），TEWL增加了（1.12±0.2）倍，而皮肤脂质过氧化增加了1.4倍（p<0.05）。丙胺卡因使百草枯的透皮渗透率增加（ER=2.1±0.4，p<0.05），但避蚊胺、2,4-D和DMF的吸收不受血流量增加的影响。用肾上腺素减少皮肤血流量并未导致透皮渗透率发生任何显著变化。
单次摄入乙醇引发的血管舒张并非观察到的透皮吸收增加的原因。乙醇诱导的脂质过氧化和TEWL变化表明，饮酒会诱导外源性物质的透皮吸收。
