Riesenhuber Andrea, Kasper David C, Vargha Regina, Endemann Michaela, Aufricht Christoph
Department of Pediatrics, Medical University of Vienna, Kinderdialyse, Universitaetsklinik fuer Kinder-und Jugendheilkunde, Waehringer Guertel 18-20, 1090, Wien, Austria.
Pediatr Nephrol. 2007 Aug;22(8):1205-8. doi: 10.1007/s00467-007-0484-4. Epub 2007 Apr 25.
During peritoneal dialysis, mesothelial cells have been shown to undergo severe damage due to continuous exposure to peritoneal dialysis fluid (PDF) with cytotoxic physicochemical properties. In this study, we investigated the cytoprotective role of the bioflavonoid Quercetin in the in vitro model of peritoneal dialysis. Immortalized human mesothelial cells (Met5A) were exposed either to regular growth medium or to standard acidic lactate-buffered PDF (Dianeal PD4) or to a more biocompatible lactate-bicarbonate-buffered PDF (Physioneal 40). Parallel cell cultures were supplemented with 200 microM Quercetin. Cytotoxicity was assessed qualitatively by morphologic assessment and quantitatively by the release of cytoplasmic lactate dehydrogenase and fluorescence-activated cell sorting (FACS). PDF exposure with bioincompatible Dianeal PD4 resulted in severe disruption of cell cultures and in significantly increased lactate dehydrogenase (LDH) release (p=0.0007 vs. control). Addition of 200 microM Quercetin significantly decreased the LDH release (p=0.04 vs. "pure" Dianeal PD4 exposure), comparable to control exposure and to more biocompatible Physioneal 40 exposure (p=0.37) and resulted in marked preservation of cell culture monolayers and cellular viability as assessed by FACS. Introduction of cytoprotective agents such as Quercetin may represent an alternate approach to protect mesothelial cells from cytotoxicity of frequently used PDFs, comparably effective to the introduction of novel, more biocompatible, PDFs.
在腹膜透析过程中，间皮细胞已被证明会因持续暴露于具有细胞毒性物理化学特性的腹膜透析液（PDF）而遭受严重损伤。在本研究中，我们在腹膜透析的体外模型中研究了生物类黄酮槲皮素的细胞保护作用。将永生化的人腹膜间皮细胞（Met5A）分别暴露于常规生长培养基、标准酸性乳酸缓冲PDF（百特PD4）或生物相容性更好的乳酸 - 碳酸氢盐缓冲PDF（百特40）。平行的细胞培养物中添加了200微摩尔的槲皮素。通过形态学评估定性评估细胞毒性，并通过细胞质乳酸脱氢酶的释放和荧光激活细胞分选（FACS）定量评估。与生物不相容的百特PD4接触会导致细胞培养严重破坏，乳酸脱氢酶（LDH）释放显著增加（与对照组相比，p = 0.0007）。添加200微摩尔的槲皮素显著降低了LDH的释放（与“单纯”百特PD4接触相比，p = 0.04），与对照接触和生物相容性更好的百特40接触相当（p = 0.37），并通过FACS评估显示细胞培养单层和细胞活力得到显著保留。引入诸如槲皮素等细胞保护剂可能是保护间皮细胞免受常用PDF细胞毒性影响的另一种方法，其效果与引入新型、生物相容性更好的PDF相当。
