Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants
Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants
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DOI：
10.1007/s00240-002-0286-x
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发表时间：
2003-03-01
影响因子：
--
通讯作者：
Menon, M
中科院分区：
文献类型：
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作者：
Thamilselvan, S;Khan, SR;Menon, M
在之前的研究中，我们证明了草酸诱导的自由基损伤可以促进草酸钙结石的形成。在本研究中，我们测试了抗氧化剂维生素E、超氧化物歧化酶（SOD）、过氧化氢酶和去铁胺（DFO）是否能保护LLC-PK1细胞免受草酸盐的毒性。将LLC-PK1细胞暴露于草酸盐（1.0 mM）或草酸盐+草酸钙一水晶体（COM, 500 μ m）中3、6和9小时。通过乳酸脱氢酶（LDH）释放来评估细胞损伤。测定丙二醛（MDA）含量、过氧化氢酶和谷胱甘肽过氧化物酶活性。考察了维生素E （200 muM）、DFO （1.0 mM）、SOD （400 U）和过氧化氢酶（400 U）对草酸暴露细胞的影响。暴露于草酸盐的LLC-PK1细胞LDH释放量和MDA含量显著增加，添加COM晶体后进一步升高。草酸降低了细胞谷胱甘肽过氧化物酶和过氧化氢酶的活性。添加维生素E、SOD、过氧化氢酶和DFO显著降低了乳酸脱氢酶的释放，使谷胱甘肽过氧化物酶和过氧化氢酶活性恢复到对照水平。在抗氧化剂和抗氧化酶的作用下，草酸或草酸+ COM中毒时MDA生成的增加恢复到正常水平。维生素E的保护作用大于SOD、过氧化氢酶和DFO。我们得出结论，草酸盐相关的自由基损伤可能通过为晶体成核和聚集提供细胞碎片和增加晶体与其他管状细胞的附着来促进结石的形成。抗氧化剂可以通过防止草酸介导的过氧化损伤来阻止草酸钙在肾小管中的成核和滞留。
In a previous study we demonstrated that oxalate induced free radical injury can promote calcium oxalate stone formation. In the present study, we tested whether the antioxidants vitamin E, superoxide dismutase (SOD), catalase and desferoxamine (DFO) can provide protection against oxalate toxicity in LLC-PK1 cells. LLC-PK1 cells were exposed to oxalate (1.0 mM) or oxalate + calcium oxalate monohydrate crystals (COM, 500 mugm) for 3, 6, and 9 h. Cellular injury was assessed by lactate dehydrogenase (LDH) release. Malondialdehyde (MDA) content, catalase and glutathione peroxidase activities were also measured. The effect of vitamin E (200 muM), DFO (1.0 mM), SOD (400 U), and catalase (400 U) on oxalate-exposed cells was tested. LLC-PK1 cells exposed to oxalate showed a significant increase in LDH release and MDA content, which was further elevated when COM crystals were added. Cellular glutathione peroxidase and catalase activities were decreased on exposure to oxalate. The addition of vitamin E, SOD, catalase and DFO significantly reduced the release of LDH and restored glutathione peroxidase and catalase activities towards the control level. The increased formation of MDA on oxalate or oxalate + COM toxicity was restored towards normalization by antioxidants and antioxidant enzymes. The protection rendered by vitamin E was greater than that of SOD, catalase and DFO. We conclude that oxalate associated free radical injury may promote stone formation by providing cellular debris for crystal nucleation and aggregation and augment crystal attachment to other tubular cells. Antioxidant administration may prevent calcium oxalate nucleation and retention in the renal tubules by preventing oxalate mediated peroxidative injury.