Jaeschke H
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Am J Physiol. 1990 Apr;258(4 Pt 1):G499-505. doi: 10.1152/ajpgi.1990.258.4.G499.
Formation of glutathione disulfide (GSSG) was used as an index of reactive oxygen generation in the isolated perfused liver of male Fischer rats during normoxia and hypoxia. Low oxygen tension may affect GSSG formation, rereduction, and transport mechanisms. The effect of short-term hypoxia (15 min) on the biliary and sinusoidal transport of GSSG was tested with the glutathione S-conjugates of sulfobromophthalein and 1-chloro-2,4-dinitrobenzene. Hypoxia inhibited S-conjugate excretion through both pathways by 15-20%. tert-Butyl hydroperoxide (75 microM tBHP) or diquat (200 microM) in the perfusate increased hepatic GSSG release by 430 and 1,550%, respectively, and increased the tissue GSSG content by 47 and 124%, respectively, under normoxia. Hypoxia reduced the stimulated GSSG export by 38 (tBHP) and 83% (diquat) and also caused an additional increase of the tissue GSSG content by 112% during tBHP infusion but caused a reduction by 32% during diquat infusion. Inhibition of the biliary export of GSSG and S-conjugates is mainly compensated by the sinusoidal efflux. Therefore, it is concluded that hypoxia reduces GSSG formation predominantly through suppression of reactive oxygen formation with only marginal effects on the biliary and sinusoidal excretion mechanism. Thus hepatic GSSG formation is a sensitive indicator of oxidant stress during normoxia and hypoxia. Because single parameters may vary considerably, simultaneous monitoring of GSSG in bile, perfusate, and tissue is essential for qualitative and quantitative estimation of reactive oxygen formation.
在常氧和低氧条件下，以谷胱甘肽二硫化物（GSSG）的形成作为雄性Fischer大鼠离体灌注肝脏中活性氧生成的指标。低氧张力可能影响GSSG的形成、再还原和转运机制。用磺溴酞钠和1-氯-2,4-二硝基苯的谷胱甘肽S-共轭物测试短期低氧（15分钟）对GSSG胆汁和窦状隙转运的影响。低氧使通过这两种途径的S-共轭物排泄减少15%-20%。在常氧条件下，灌注液中的叔丁基过氧化氢（75μM tBHP）或百草枯（200μM）分别使肝脏GSSG释放增加430%和1550%，并使组织GSSG含量分别增加47%和124%。低氧使tBHP刺激的GSSG输出减少38%（tBHP）和83%（百草枯），并且在tBHP输注期间还使组织GSSG含量额外增加112%，但在百草枯输注期间使组织GSSG含量减少32%。GSSG和S-共轭物胆汁输出的抑制主要由窦状隙流出补偿。因此，得出结论，低氧主要通过抑制活性氧的形成来减少GSSG的形成，对胆汁和窦状隙排泄机制的影响很小。因此，肝脏GSSG的形成是常氧和低氧期间氧化应激的敏感指标。由于单个参数可能有很大差异，同时监测胆汁、灌注液和组织中的GSSG对于活性氧形成的定性和定量评估至关重要。
