Formation of ethyl nitrite in vivo after ethanol administration.
Formation of ethyl nitrite in vivo after ethanol administration.
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DOI：
10.1016/j.alcohol.2004.09.005
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发表时间：
2004-10
期刊：
影响因子：
2.3
通讯作者：
Xin-sheng Deng;P. Bludeau;R. Deitrich
中科院分区：
文献类型：
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作者：
Xin-sheng Deng;P. Bludeau;R. Deitrich
本研究的目的是确定是否可以在体外检测到亚硝酸乙酯从乙醇与过氧亚硝酸盐的反应，以及乙醇给药后的小鼠。采用固相微萃取-顶空气相色谱-质谱联用技术测定亚硝酸乙酯。过氧亚硝酸盐被允许在各种条件下与乙醇在体外反应。过氧亚硝酸盐与乙醇反应生成亚硝酸乙酯。雄性近交系短睡眠小鼠腹腔注射乙醇[5.2 g/kg; 15.0%（重量/体积）乙醇的盐水溶液]或氘标记乙醇（D5-乙醇）和乙醇的50：50混合物。30分钟后，从小鼠获得血液样品以及全脑和肝切片，用于测定乙醇、D5-乙醇、亚硝酸乙酯和氘标记的亚硝酸乙酯（D5-亚硝酸乙酯）。进行了从小鼠获得的血液样品以及全脑和肝切片中亚硝酸乙酯出现的时间过程。乙醇给药后，在小鼠血液、脑和肝脏中检测并定量亚硝酸乙酯。存在一小部分亚硝酸乙酯。当将乙醇和D5-乙醇的50：50混合物给予动物时，在血液和脑中发现亚硝酸乙酯和D5-亚硝酸乙酯的比例与乙醇和D5-乙醇的比例大致相同。D5-亚硝酸乙酯在肝脏中的水平是亚硝酸乙酯的两倍多，表明亚硝酸乙酯代谢中可能存在同位素效应。亚硝酸乙酯是乙醇在体内的新代谢产物。亚硝酸乙酯形成的机制最有可能是乙醇与体内由一氧化氮产生的过氧亚硝酸盐反应。
The purpose of the current study was to ascertain whether ethyl nitrite could be detected in vitro from the reaction of ethanol with peroxynitrite, as well as after administration of ethanol to mice. Ethyl nitrite analyte was determined by using gas chromatography–mass spectrometry with headspace analysis with the use of a solid-phase microextraction device. Peroxynitrite was allowed to react with ethanol under a variety of conditions in vitro. Ethyl nitrite was generated when peroxynitrite was allowed to react with ethanol. Male, inbred short-sleep mice were injected intraperitoneally with either ethanol [5.2 g/kg; 15.0% (weight/volume) ethanol in saline] or a 50:50 mixture of deuterium-labeled ethanol (D5-ethanol) and ethanol. Blood samples, as well as whole brain and liver sections, were obtained from mice 30 min later for determination of ethanol, D5-ethanol, ethyl nitrite, and deuterium-labeled ethyl nitrite (D5-ethyl nitrite). Time courses for the appearance of ethyl nitrite in blood samples, as well as in whole brain and liver sections, obtained from mice were carried out. After ethanol administration, ethyl nitrite was detected and quantitated in mouse blood, brain, and liver. A small fraction of ethyl nitrite was present. When a 50:50 mixture of ethanol and D5-ethanol was given to animals, both ethyl nitrite and D5-ethyl nitrite were found in blood and brain in approximately the same ratio as that of ethanol and D5-ethanol. The level of D5-ethyl nitrite in liver was more than twice that of ethyl nitrite, indicating a possible isotope effect in the metabolism of ethyl nitrite. Ethyl nitrite is a new metabolite of ethanol in vivo. The mechanism of ethyl nitrite formation is most likely the reaction of ethanol with peroxynitrite generated in vivo from nitric oxide.