Mahiout A, Matata B M, Brunkhorst R
Institute of Cell and Protein Engineering, Medical School Hannover, Germany.
Kidney Int. 1997 Mar;51(3):860-7. doi: 10.1038/ki.1997.121.
A new peritoneal dialysate containing pyruvate anions has been tested for its effects on cell functions and compared with conventional lactate and bicarbonate based solutions. The dialysate has a final pH of 5.4 to 5.6 and is composed of 1.36 to 3.86% glucose-monohydrate, 132 mmol/liter sodium, 1.75 mmol/liter calcium, 0.75 mmol/liter magnesium, 102 mmol/liter chloride and 35 mmol/liter pyruvate. For cytotoxicity testing peritoneal macrophages and peripheral blood mononuclear cells (PBMC) were exposed to conventional lactate dialysate, pyruvate dialysate, bicarbonate dialysate and a control medium RPMI 1640 (Biochrom KG, Berlin, Germany), followed by activation with different bacterial stimuli. In addition, the study further investigated the effect of varying glucose concentration in the different dialysates ranging from 0 to 3.86% and pH changes between 5.2 and 7.4 on the cytotoxicity effect on the selected cells. Mononuclear cells exposed to pyruvate-based dialysate before stimulation with endotoxin exhibited a tumor necrosis factor (TNF)-mRNA signal comparable to those of cells exposed to RPMI. In contrast, exposure to lactate-based dialysate completely inhibited TNF-mRNA synthesis. In addition, cytokine synthesis in macrophages and PBMCs after exposure to pyruvate was less inhibited when compared to the corresponding levels measured after exposure to lactate. The chemotactic response of polymorphonuclear cells and O-2 generation in all tested cell types after exposure to pyruvate was found not to be inhibited, whereas a complete inhibition was observed after exposure to lactate. The results demonstrate that cytotoxicity effects of peritoneal dialysate on cell lines can be minimized by using a new dialysate formulation containing pyruvate anions instead of lactate.
一种含有丙酮酸阴离子的新型腹膜透析液已针对其对细胞功能的影响进行了测试,并与传统的基于乳酸盐和碳酸氢盐的溶液进行了比较。该透析液的最终pH值为5.4至5.6,由1.36%至3.86%的一水葡萄糖、132 mmol/升钠、1.75 mmol/升钙、0.75 mmol/升镁、102 mmol/升氯和35 mmol/升丙酮酸组成。为了进行细胞毒性测试,将腹膜巨噬细胞和外周血单核细胞(PBMC)暴露于传统乳酸盐透析液、丙酮酸透析液、碳酸氢盐透析液和对照培养基RPMI 1640(德国柏林Biochrom KG公司)中,随后用不同的细菌刺激物进行激活。此外,该研究进一步调查了不同透析液中葡萄糖浓度从0到3.86%的变化以及pH值在5.2至7.4之间的变化对所选细胞细胞毒性作用的影响。在内毒素刺激之前暴露于基于丙酮酸的透析液的单核细胞表现出与暴露于RPMI的细胞相当的肿瘤坏死因子(TNF)-mRNA信号。相比之下,暴露于基于乳酸盐的透析液会完全抑制TNF-mRNA的合成。此外,与暴露于乳酸盐后测量的相应水平相比,暴露于丙酮酸后巨噬细胞和PBMC中的细胞因子合成受到的抑制较小。发现暴露于丙酮酸后所有测试细胞类型中多形核细胞的趋化反应和O-2生成均未受到抑制,而暴露于乳酸盐后则观察到完全抑制。结果表明,通过使用含有丙酮酸阴离子而非乳酸盐的新型透析液配方,可以将腹膜透析液对细胞系的细胞毒性作用降至最低。