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首页> 外文期刊>Journal of biochemical and molecular toxicology >New insights into the mechanisms involved in renal proximal tubular damage induced in vitro by ochratoxin A.
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New insights into the mechanisms involved in renal proximal tubular damage induced in vitro by ochratoxin A.

机译：对曲霉毒素A体外诱导的肾近端肾小管损伤相关机制的新见解。

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摘要

The mycotoxin ochratoxin A is a contaminant of human and animal food products. It is a potent nephrotoxin known to damage the proximal tubule. The aim of this work was to investigate the effects of ochratoxin A on a porcine renal proximal tubular epithelial cell line (LLC-PK1), and to identify sensitive endpoints revealing damage at the epithelial barrier level and at the molecular level. Cells exposed for 24 h to 5-10 microM ochratoxin indicated a clear damage to the intactness of the epithelial barrier, as shown by measurements of trans-epithelial resistance and zonula occludens-1 protein expression. At the mitochondrial level we observed alterations of the normal functions, such as an increase of the membrane potential, the formation of straight extensions, and the formation of giant mitochondria. At higher ochratoxin concentrations (50 microM), at which cytotoxicity assays revealed a significant toxicity, alterations of the cytoskeleton organization and induction of apoptosis were evident. In addition, we analyzed the expression of genes by using a cDNA macroarray. Our data indicate that ochratoxin-induced nephrotoxicity can be detected at the barrier and at the mitochondrial level at rather low concentrations, at which conventional cytotoxicity assays are unable to reveal toxic effects.
机译：霉菌毒素曲霉毒素A是人类和动物食品的污染物。它是一种有效的肾毒素，已知会损害近端小管。这项工作的目的是研究曲霉毒素A对猪肾近端肾小管上皮细胞系（LLC-PK1）的影响，并确定在上皮屏障水平和分子水平揭示损伤的敏感终点。暴露于5-10 microM ra曲霉毒素24 h的细胞表明对上皮屏障的完整性有明显损害，如通过跨上皮耐药性和小带闭合蛋白1蛋白表达的测量所示。在线粒体水平上，我们观察到正常功能的改变，例如膜电位的增加，直线延伸的形成以及巨大的线粒体的形成。在较高的ra曲霉毒素浓度（50 microM）下，细胞毒性测定显示出明显的毒性，细胞骨架组织的改变和凋亡的诱导是显而易见的。此外，我们通过使用cDNA宏阵列分析了基因的表达。我们的数据表明曲霉毒素诱导的肾毒性可以在屏障和线粒体水平上以相当低的浓度检测到，在常规浓度下，常规的细胞毒性试验无法揭示其毒性作用。

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