Burgunder J M, Lauterburg B H
Department of Clinical Pharmacology, University of Berne, Switzerland.
Eur J Clin Invest. 1987 Oct;17(5):408-14. doi: 10.1111/j.1365-2362.1987.tb01135.x.
Studies in animals have demonstrated the central role of the liver in regulating the circulating pool of glutathione (GSH). Most of the hepatic GSH production is released into blood and most of the circulating GSH originates in the liver. We have estimated the production of GSH in eight healthy volunteers and eight patients with cirrhosis by an analysis of the kinetics of plasma GSH. The basal plasma concentrations of free GSH were 9.3 +/- 2.4 microM in healthy volunteers and 3.6 +/- 1.1 microM in cirrhotics (P less than 0.001), and the concentrations of total GSH 16.6 +/- 6.2 microM in control subjects and 7.1 +/- 2.6 microM in cirrhotics (P less than 0.002). The concentration of GSH in the circulating pool depends on the input of GSH into this compartment and is inversely proportional to the volume of distribution of GSH (Vd) and to the fractional rate of elimination of GSH from plasma (kel). Assuming that the kinetics of endogenously produced and exogenously administered GSH are identical, Vd and kel can be calculated from the plasma concentration-time curve of a single i.v. injection of GSH. Both Vd (0.100 +/- 0.044 l kg-1 in controls and 0.131 +/- 0.043 l kg-1 in cirrhotics) and kel (0.2718 +/- 0.0555 min-1 in controls and 0.2912 +/- 0.0781 min-1 in cirrhotics) were identical in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
对动物的研究表明，肝脏在调节谷胱甘肽（GSH）循环池方面起着核心作用。肝脏产生的大部分GSH会释放到血液中，而循环中的大部分GSH都源自肝脏。我们通过分析血浆GSH的动力学，估算了8名健康志愿者和8名肝硬化患者体内GSH的生成情况。健康志愿者的游离GSH基础血浆浓度为9.3±2.4微摩尔/升，肝硬化患者为3.6±1.1微摩尔/升（P＜0.001）；对照组总GSH浓度为16.6±6.2微摩尔/升，肝硬化患者为7.1±2.6微摩尔/升（P＜0.002）。循环池中GSH的浓度取决于进入该隔室的GSH输入量，并且与GSH的分布容积（Vd）以及GSH从血浆中消除的分数速率（kel）成反比。假设内源性产生和外源性给予的GSH动力学相同，则可以根据单次静脉注射GSH后的血浆浓度-时间曲线计算Vd和kel。两组的Vd（对照组为0.100±0.044升/千克，肝硬化患者为0.131±0.043升/千克）和kel（对照组为0.2718±0.0555分钟-1，肝硬化患者为0.2912±0.0781分钟-1）相同。（摘要截短于250字）
