Grattagliano I, Wieland P, Schranz C, Lauterburg B H
Department of Clinical Pharmacology, University of Bern, Schweiz.
Pharmacol Toxicol. 1994 Dec;75(6):343-7. doi: 10.1111/j.1600-0773.1994.tb00372.x.
Glutathione (GSH) plays an important role in the detoxification of reactive metabolites of oxygen and xenobiotics and as a source of cysteine. Since several clinical situations characterized by low circulating and intracellular GSH have been identified, there is a growing interest in pharmacological interventions to correct a deranged sulfhydril status. Therefore, the systemic bioavailability of orally administered GSH and glutathione monoethyl ester (GSHE) was examined in the rat. Following the intraduodenal administration of 0.5 mmol/kg of GSH and GSHE there was no significant increase in the concentrations of cysteine and GSH in plasma, but hepatic cysteine and GSH increased significantly, albeit transiently. Five mmol/kg of GSH and GSHE significantly increased circulating and hepatic cysteine and GSH. Following the administration of 0.5 and 5 mmol/kg of GSHE low concentrations of the ester were found in plasma and the liver, indicating that GSHE is not readily absorbed from the gastrointestinal tract, although it is not a substrate for gamma-glutamyl-transferase. GSHE resulted in a delayed release of cysteine and GSH compared to GSH, such that the concentrations of GSH and cysteine in liver and plasma were significantly higher 2 h after administration of GSHE than after GSH. The data indicate that the bioavailability of GSH and GSHE is low in the rat. Orally administered GSH and GSHE do not affect the circulating concentrations of GSH and cysteine unless very high doses are administered, but increase hepatic cysteine and GSH at lower doses because of the efficient extraction by the liver of cysteine originating from the breakdown of GSH and GSHE in the gut.
谷胱甘肽（GSH）在氧的反应性代谢产物和外源性物质的解毒过程中以及作为半胱氨酸的来源发挥着重要作用。由于已经确定了几种以循环和细胞内GSH水平低为特征的临床情况，人们对纠正紊乱的巯基状态的药物干预的兴趣日益增加。因此，在大鼠中研究了口服GSH和谷胱甘肽单乙酯（GSHE）的全身生物利用度。十二指肠内给予0.5 mmol/kg的GSH和GSHE后，血浆中半胱氨酸和GSH的浓度没有显著增加，但肝脏中的半胱氨酸和GSH显著增加，尽管是短暂的。5 mmol/kg的GSH和GSHE显著增加了循环和肝脏中的半胱氨酸和GSH。给予0.5和5 mmol/kg的GSHE后，在血浆和肝脏中发现了低浓度的酯，这表明GSHE不易从胃肠道吸收，尽管它不是γ-谷氨酰转移酶的底物。与GSH相比，GSHE导致半胱氨酸和GSH的释放延迟，因此在给予GSHE后2小时，肝脏和血浆中GSH和半胱氨酸的浓度显著高于给予GSH后。数据表明，GSH和GSHE在大鼠中的生物利用度较低。口服GSH和GSHE除非给予非常高的剂量，否则不会影响GSH和半胱氨酸的循环浓度，但在较低剂量下会增加肝脏中的半胱氨酸和GSH，这是因为肝脏对源自肠道中GSH和GSHE分解的半胱氨酸有高效的摄取。
