Jonen H G
Drug Metab Dispos. 1979 May-Jun;7(3):176-80.
Reductive metabolism of p-nitrobenzoate (2 mM) was studied in the isolated perfused rat liver, after acute ethanol dosing, with use of a hemoglobin-free perfusion medium. Formation of reduced metabolites under control conditions (0.3 mumol per g of liver per hr) was enhanced fivefold (1.4 mumol/g/hr) in the presence of ethanol (38 mM), thus reaching hepatic reductase activities occurring under anaerobic conditions (1.4 mumol/g/hr). Ethanol failed to increase hepatic nitro reduction when alcohol dehydrogenase was inhibited by pyrazole. Addition of acetaldehyde led to a marked stimulation of nitroreductase activity. Carbon monoxide did not influence the ethanol-mediated enhancement of nitroreductase activity but almost abolished the enhancement caused by anoxia. Reductive azo cleavage of salazosulfamide was not enhanced by ethanol. When nitrazepam was used as the substrate (1 mM) for the isolated perfused rat liver, addition of ethanol (38 mM) led to an enhanced content of 7-amino derivative in the liver and in the perfusate, whereas the formation of 7-acetylamino derivative remained unchanged. The distribution of nitrazepam in liver and perfusate was not altered by ethanol.
在急性给予乙醇后，使用无血红蛋白灌注培养基，在离体灌注大鼠肝脏中研究了对硝基苯甲酸盐（2 mM）的还原代谢。在对照条件下（每克肝脏每小时0.3微摩尔）还原代谢产物的形成，在存在乙醇（38 mM）的情况下增加了五倍（1.4微摩尔/克/小时），从而达到在厌氧条件下发生的肝脏还原酶活性（1.4微摩尔/克/小时）。当吡唑抑制乙醇脱氢酶时，乙醇未能增加肝脏硝基还原。添加乙醛导致硝基还原酶活性显著刺激。一氧化碳不影响乙醇介导的硝基还原酶活性增强，但几乎消除了缺氧引起的增强。乙醇未增强柳氮磺胺的还原性偶氮裂解。当硝西泮用作离体灌注大鼠肝脏的底物（1 mM）时，添加乙醇（38 mM）导致肝脏和灌注液中7-氨基衍生物的含量增加，而7-乙酰氨基衍生物的形成保持不变。乙醇未改变硝西泮在肝脏和灌注液中的分布。
