Yeung John H K, Or Penelope M Y
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Food Chem Toxicol. 2007 Jun;45(6):953-61. doi: 10.1016/j.fct.2006.12.005. Epub 2006 Dec 14.
The effects of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of PSP (1-4 micromole/kg, i.p.) produced a transient, dose-dependent depletion (10-37%) of hepatic GSH, with no effect on serum glutamic-pyruvic transaminase (SGPT) activity. Blood GSH was depleted (6-25%) at 3 h, followed by a rebound increase above the control GSH level (20%) at 18 h. The GSSG/GSH ratio, a measure of oxidative stress, was increased 3 h after PSP treatment but returned to normal levels at 24 h. Sub-chronic treatment of PSP (1-4 micromole/kg/day, i.p.) for seven days did not produce any significant changes in hepatic GSH levels and the GSSG/GSH ratio when measured 24 h after the final dose of PSP. PSP had little effect on glutathione transferase (GST), glutathione reductase (GSSG reductase) and glutathione peroxidase (GPX) activities in the liver. However, a dose-dependent increase in blood GPX activity (30-48%) was observed at 3h, which coincided with the increase in the GSSG/GSH ratio. The increase in blood GPX activity may be a responsive measure to deal with the transient oxidative stress induced by PSP treatment. The results showed that PSP only caused a transient perturbation on hepatic glutathione without affecting the GSH-related enzymes such as GST, GSSG reductase and GPX. The observed changes in blood GSH simply reflected the intra-organ translocation of glutathione, as the glutathione-related enzymes were not significantly affected by PSP treatment.
研究了从云芝COV - 1中分离出的免疫调节剂多糖肽(PSP)对C57小鼠谷胱甘肽(GSH)及GSH相关酶的影响。腹腔注射PSP(1 - 4微摩尔/千克)可使肝脏GSH产生短暂的、剂量依赖性消耗(10 - 37%),对血清谷丙转氨酶(SGPT)活性无影响。血液GSH在3小时时减少(6 - 25%),随后在18小时时反弹升高至高于对照GSH水平(20%)。作为氧化应激指标的GSSG/GSH比值在PSP处理后3小时升高,但在24小时时恢复至正常水平。连续7天腹腔注射亚慢性剂量的PSP(1 - 4微摩尔/千克/天),在最后一剂PSP给药24小时后测量,肝脏GSH水平和GSSG/GSH比值未产生任何显著变化。PSP对肝脏中的谷胱甘肽转移酶(GST)、谷胱甘肽还原酶(GSSG还原酶)和谷胱甘肽过氧化物酶(GPX)活性影响很小。然而,在3小时时观察到血液中GPX活性呈剂量依赖性增加(30 - 48%),这与GSSG/GSH比值的增加一致。血液中GPX活性的增加可能是应对PSP处理诱导的短暂氧化应激的一种反应措施。结果表明,PSP仅对肝脏谷胱甘肽造成短暂扰动,而不影响GST、GSSG还原酶和GPX等GSH相关酶。观察到的血液GSH变化仅仅反映了谷胱甘肽在器官内的转运,因为谷胱甘肽相关酶未受到PSP处理的显著影响。