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单次高口服剂量后大鼠模型中乙醇向乙基葡萄糖醛酸苷的生物转化。

Biotransformation of ethanol to ethyl glucuronide in a rat model after a single high oral dosage.

机构信息

Section of Toxicology, East Tennessee State University, Johnson City, TN 37614, USA.

出版信息

Alcohol. 2012 Mar;46(2):159-64. doi: 10.1016/j.alcohol.2011.07.006. Epub 2011 Oct 21.

DOI:10.1016/j.alcohol.2011.07.006
PMID:22019193
Abstract

Ethyl glucuronide (EtG) is a minor ethanol metabolite that confirms the absorption and metabolism of ethanol after oral or dermal exposure. Human data suggest that maximum blood EtG (BEtG) concentrations are reached between 3.5 and 5.5h after ethanol administration. This study was undertaken to determine if the Sprague-Dawley (SD) rat biotransforms ethanol to EtG after a single high oral dose of ethanol. SD rats (male, n=6) were gavaged with a single ethanol dose (4 g/kg), and urine was collected for 3 h in metabolic cages, followed by euthanization and collection of heart blood. Blood and urine were analyzed for ethanol and EtG by gas chromatography and enzyme immunoassay. Blood and urine ethanol concentrations were 195±23 and 218±19 mg/dL, whereas BEtG and urine EtG (UEtG) concentrations were 1,363±98 ng equivalents/mL and 210±0.29 mg equivalents/dL (X ± standard error of the mean [S.E.M.]). Sixty-six male SD rats were gavaged ethanol (4 g/kg) and placed in metabolic cages to determine the extent and duration of ethanol to EtG biotransformation and urinary excretion. Blood and urine were collected up to 24 h after administration for ethanol and EtG analysis. Maximum blood ethanol, urine ethanol, and UEtG were reached within 4 h, whereas maximum BEtG was reached 6 h after administration. Maximum concentrations were blood ethanol, 213±20 mg/dL; urine ethanol, 308±34 mg/dL; BEtG, 2,683±145 ng equivalents/mL; UEtG, 1.2±0.06 mg equivalents/mL (X±S.E.M.). Areas under the concentration-time curve were blood ethanol, 1,578 hmg/dL; urine ethanol, 3,096 hmg/dL; BEtG, 18,284 hng equivalents/mL; and UEtG, 850 hmg equivalents/dL. Blood ethanol and BEtG levels were reduced to below limits of detection (LODs) within 12 and 18 h after ethanol administration. Urine ethanols were below LOD at 18 h, but UEtG was still detectable at 24h after administration. Our data prove that the SD rat biotransforms ethanol to EtG and excretes both in the urine and suggest that it is similar to that of the human.

摘要

乙基葡萄糖醛酸苷(EtG)是一种微量乙醇代谢物,可证实口服或皮肤接触乙醇后的吸收和代谢。人体数据表明,乙醇给药后最大血 EtG(BEtG)浓度在 3.5 至 5.5 小时达到。本研究旨在确定单次高口服乙醇剂量后,Sprague-Dawley(SD)大鼠是否会将乙醇转化为 EtG。雄性 SD 大鼠(n=6)经灌胃给予单剂量乙醇(4 g/kg),在代谢笼中收集 3 小时尿液,然后处死并采集心血。通过气相色谱和酶免疫分析法分析血液和尿液中的乙醇和 EtG。血液和尿液中的乙醇浓度分别为 195±23 和 218±19mg/dL,而 BEtG 和尿液 EtG(UEtG)浓度分别为 1363±98ng 当量/mL 和 210±0.29mg 当量/dL(X±平均值的标准误差[SEM])。66 只雄性 SD 大鼠经灌胃给予乙醇(4 g/kg)并置于代谢笼中,以确定乙醇转化为 EtG 和尿排泄的程度和持续时间。给药后 24 小时内采集血液和尿液进行乙醇和 EtG 分析。血液乙醇、尿液乙醇和 UEtG 在 4 小时内达到最大值,而 BEtG 在给药后 6 小时达到最大值。最大浓度为血液乙醇,213±20mg/dL;尿液乙醇,308±34mg/dL;BEtG,2683±145ng 当量/mL;UEtG,1.2±0.06mg 当量/mL(X±SEM)。血乙醇浓度-时间曲线下面积为 1578hmg/dL;尿液乙醇浓度-时间曲线下面积为 3096hmg/dL;BEtG 浓度-时间曲线下面积为 18284hng 当量/mL;UEtG 浓度-时间曲线下面积为 850hmg 当量/dL。血液乙醇和 BEtG 水平在乙醇给药后 12 至 18 小时内降至检测限(LOD)以下。尿液乙醇在 18 小时时低于 LOD,但 UEtG 在给药后 24 小时仍可检测到。我们的数据证明 SD 大鼠将乙醇转化为 EtG 并在尿液中排泄,这表明它与人类相似。

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