Oxalate is toxic to renal tubular cells only at supraphysiologic concentrations
Oxalate is toxic to renal tubular cells only at supraphysiologic concentrations
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DOI：
10.1111/j.1523-1755.2005.00576.x
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发表时间：
2005-10-01
影响因子：
19.6
通讯作者：
Verkoelen, CF
中科院分区：
文献类型：
--
作者：
Schepers, MSJ;van Ballegooijen, ES;Verkoelen, CF
草酸盐仅在超生理浓度时对肾小管细胞有毒性。草酸盐诱导的组织损伤可能在草酸钙肾结石的病理生理学中起起始作用。肾集合管中的草酸盐浓度（类似于0.1至0.5 mmol/L）高于近端小管中的草酸盐浓度（类似于0.002至0.1 mmol/L）。本实验研究了草酸对体外培养的肾近曲小管和集合小管细胞的损伤作用。使用肾近端小管细胞系LLC-PK 1和Madin达比犬肾II（MDCK-II）以及肾集合管细胞系大鼠肾皮质集合管（RCCD 1）和MDCK-I进行研究。在两室培养系统中，在可渗透生长基质上培养的汇合单层细胞顶部暴露于相对低浓度的（0.2、0.5和1.0 mmol/L）和高（5和10 mmol/L）草酸盐浓度，之后研究了几种细胞反应，包括单层形态（共聚焦显微镜）、跨上皮电阻（TER）、前列腺素E-2（PGE（2））分泌、乳酸脱氢酶（LDH）释放、DNA合成（[H-3]-胸苷掺入）、总细胞数、活性氧（H2 O2）产生、凋亡（膜联蛋白V和DNA片段化）和坏死（碘化丙啶流入）细胞死亡。可见的形态学改变，观察到只有在高草酸浓度。TER是浓度依赖性降低高，但不是由低，草酸。暴露于高草酸盐后，两种细胞类型中的PGE（2）、LDH和H2 O2水平均升高，但暴露于低草酸盐后未升高。暴露于高草酸导致DNA合成水平升高，总细胞数减少。高浓度草酸诱导的坏死细胞死亡没有程序性细胞死亡的迹象，而低浓度草酸诱导的坏死细胞死亡没有程序性细胞死亡的迹象。这项研究表明，草酸对肾小管细胞是有毒的，但仅在超生理浓度。
Oxalate is toxic to renal tubular cells only at supraphysiologic concentrations.Background. Oxalate-induced tissue damage may play an initiating role in the pathophysiology of calcium oxalate nephrolithiasis. The concentration of oxalate is higher in the renal collecting ducts (similar to 0.1 to 0.5 mmol/L) than in the proximal tubule (similar to 0.002 to 0.1 mmol/L). In the present investigation, we studied the damaging effect of oxalate to renal proximal and collecting tubule cells in culture.Methods. Studies were performed with the renal proximal tubular cell lines, LLC-PK1 and Madin Darby canine kidney II (MDCK-II), and the renal collecting duct cell lines, rat renal cortical collecting duct (RCCD1) and MDCK-I. Confluent monolayers cultured on permeable growth substrates in a two-compartment culture system were apically exposed for 24 hours to relatively low (0.2, 0.5, and 1.0 mmol/L) and high (5 and 10 mmol/L) oxalate concentrations, after which several cellular responses were studied, including monolayer morphology (confocal microscopy), transepithelial electrical resistances (TER), prostaglandin E-2 (PGE(2)) secretion, lactate dehydrogenase (LDH) release, DNA synthesis ([H-3]-thymidine incorporation), total cell numbers, reactive oxygen species (H2O2) generation, apoptotic (annexin V and DNA fragmentation), and necrotic (propidium iodide influx) cell death.Results. Visible morphologic alterations were observed only at high oxalate concentrations. TER was concentration-dependently decreased by high, but not by low, oxalate. Elevated levels of PGE(2), LDH, and H2O2 were measured in both cell types after exposure to high, but not to low oxalate. Exposure to high oxalate resulted in elevated levels of DNA synthesis with decreasing total cell numbers. High, but not low, oxalate induced necrotic cell death without signs of programmed cell death.Conclusion. This study shows that oxalate is toxic to renal tubular cells, but only at supraphysiologic concentrations.