1. New insights into the mechanisms involved in renal proximal tubular damage induced in vitro by ochratoxin A.
- Author
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Gennari A, Pazos P, Boveri M, Callaghan R, Casado J, Maurici D, Corsini E, and Prieto P
- Subjects
- Animals, Cell Survival drug effects, Cytoskeleton drug effects, Gene Expression Profiling, Kidney Tubules, Proximal drug effects, LLC-PK1 Cells, Mitochondria drug effects, Oligonucleotide Array Sequence Analysis, Swine, Apoptosis drug effects, Cytoskeleton pathology, Gene Expression Regulation drug effects, Kidney Tubules, Proximal pathology, Mitochondria pathology, Ochratoxins toxicity
- Abstract
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., (Copyright 2004 Wiley Periodicals, Inc.)
- Published
- 2004
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