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New insights into the mechanisms involved in renal proximal tubular damage induced in vitro by ochratoxin A
Author(s) -
Gennari Alessandra,
Pazos Patricia,
Boveri Monica,
Callaghan Robert,
Casado Juan,
Maurici Daniela,
Corsini Emanuela,
Prieto Pilar
Publication year - 2004
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20006
Subject(s) - ochratoxin a , ochratoxin , nephrotoxicity , cytotoxicity , mycotoxin , apoptosis , toxicity , chemistry , oxidative stress , dna damage , mitochondrion , microbiology and biotechnology , in vitro , biology , biochemistry , food science , dna , organic chemistry
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 μM 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 μM), 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. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:43–49, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20006