Stepniewska Joanna, Dolegowska Barbara, Ciechanowski Kazimierz, Kwiatkowska Ewa, Millo Barbara, Chlubek Dariusz
Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.
Arch Med Res. 2006 Apr;37(3):353-9. doi: 10.1016/j.arcmed.2005.07.012.
Patients suffering from chronic renal failure (CRF) are exposed to increased oxidative stress generated by uremic toxins, factors connected with hemodialysis, chronic inflammatory state, lack of vitamins A, E and selenium, advanced age, and parenteral iron administration. Their antioxidative system is inefficient. In erythrocytes, hexosemonophosphate (HMP) cycle does not assure an adequate amount of reductive equivalents (NADPH) necessary to restore reduced glutathione (GSH), an important free radical scavenger. Hemodialysis treatment also causes a large loss of glucose, which is the basic substrate for that metabolic pathway. The object of the research was to establish the influence of glucose present in dialysate on antioxidant defense system in red blood cells.
A group of 51 patients undergoing regular hemodialysis using glucose (26 subjects, GL+ HD) or non-glucose fluid (25 subjects, GL- HD) was studied. The GSH concentration, glucose-6-phosphate dehydrogenase (G-6-P DH) and glutathione reductase (GSSG-R) activities were determined. Glucose concentration before and after the hemodialysis session was also measured.
The activity of G-6-P DH was significantly higher in GL+ HD both before (p = 0.000) and after (p = 0.0002) the dialysis treatment compared to GL- HD, respectively, and to the healthy subjects (p = 0.000). The hemodialysis session caused a decrease in the activity of the enzyme in GL+ HD from 4.91 +/- 1.53 to 4.42 +/- 1.40 U/g Hb (p = 0.004) as well as in GL- HD from 3.97 +/- 1.00 to 3.59 +/- 0.87 U/g Hb (p = 0.007). The GSSG-R showed an increase in activity in CRF patients before HD (in GL+ HD to 2.57 +/- 0.76 and in GL- HD to 2.82 +/- 0.98 U/gHb). After dialysis, lower values were observed, particularly in GL+ HD (2.05 +/- 0.59 U/g Hb, p = 0.004). GSH concentrations in the examined group were higher (in GL+ HD 0.0205 +/- 0.008 and in GL- HD 0.0196 +/- 0.008 mmol/g Hb) than in controlled subjects (0.0142 +/- 0.002 mmol/g Hb) and decreased during dialysis treatment (considerably only in GL- HD to 0.0183 +/- 0.007 mmol/g Hb, p = 0.056). Glucose concentrations in GL+ HD were significantly higher compared to GL- HD (p < 0.002).
Glucose presence in dialyzing fluid improves the HMP cycle activity as well as glutathione system reactions and determines a better antioxidant status of erythrocytes. It limits hemolysis and improves the hematological parameters in CRF.
慢性肾衰竭(CRF)患者面临着由尿毒症毒素、与血液透析相关的因素、慢性炎症状态、缺乏维生素A、E和硒、高龄以及胃肠外铁剂给药所产生的氧化应激增加的情况。他们的抗氧化系统效率低下。在红细胞中,磷酸己糖(HMP)循环无法确保产生足够数量的还原当量(NADPH)来恢复还原型谷胱甘肽(GSH),而GSH是一种重要的自由基清除剂。血液透析治疗还会导致大量葡萄糖流失,而葡萄糖是该代谢途径的基本底物。本研究的目的是确定透析液中葡萄糖对红细胞抗氧化防御系统的影响。
对一组51例接受常规血液透析的患者进行研究,其中26例使用含葡萄糖透析液(GL + HD组),25例使用无葡萄糖透析液(GL - HD组)。测定了GSH浓度、葡萄糖-6-磷酸脱氢酶(G-6-P DH)和谷胱甘肽还原酶(GSSG-R)的活性。还测量了透析前后的葡萄糖浓度。
与GL - HD组相比,GL + HD组透析前(p = 0.000)和透析后(p = 0.0002)G-6-P DH的活性均显著更高,与健康受试者相比也更高(p = 0.000)。血液透析治疗使GL + HD组该酶的活性从4.91±1.53降至4.42±1.40 U/g Hb(p = 0.004),GL - HD组从3.97±1.00降至3.59±0.87 U/g Hb(p = 0.007)。GSSG-R在HD前CRF患者中的活性增加(GL + HD组为2.57±0.76,GL - HD组为2.82±0.98 U/gHb)。透析后,观察到较低的值,尤其是GL + HD组(2.05±0.59 U/g Hb,p = 0.004)。检测组中的GSH浓度高于对照组(GL + HD组为0.0205±0.008,GL - HD组为0.0196±0.008 mmol/g Hb),而对照组为((0.0142±0.002 mmol/g Hb),且在透析治疗期间降低(仅GL - HD组显著降至0.0183±0.007 mmol/g Hb,p = 0.056)。GL + HD组的葡萄糖浓度显著高于GL - HD组(p < 0.002)。
透析液中存在葡萄糖可改善HMP循环活性以及谷胱甘肽系统反应,并确定红细胞更好的抗氧化状态。它限制了溶血并改善了CRF患者的血液学参数。