Renal epithelial gene expression profile and bismuth-induced resistance against cisplatin nephrotoxicity

Nephrotoxicity is the most important dose-limiting factor in cisplatin based anti-neoplastic treatment. Pretreatment with bismuth salts, used as pharmaceuticals to treat gastric disorders, has been demonstrated to reduce cisplatin-induced renal cell death in clinical settings and during in vivo and...

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Veröffentlicht in:Human & experimental toxicology 2003-10, Vol.22 (10), p.535-540
Hauptverfasser: Leussink, Berend T, Baelde, Hans J, den Berg, Thirza M Broekhuizen-van, de Heer, Emile, van der Voet, Gijsbert B, Slikkerveer, Anja, Bruijn, Jan A, de Wolff, Frederik A
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Sprache:eng
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Zusammenfassung:Nephrotoxicity is the most important dose-limiting factor in cisplatin based anti-neoplastic treatment. Pretreatment with bismuth salts, used as pharmaceuticals to treat gastric disorders, has been demonstrated to reduce cisplatin-induced renal cell death in clinical settings and during in vivo and in vitro animal experiments. To investigate the genomic basis of this renoprotective effect, we exposed NRK-52E cells, a cell line of rat proximal tubular epithelial origin, to 33 mM Bi3 for 12 hours, which made them resistant to cisplatin-induced apoptosis. Differentially expressed genes in treated and untreated NRK-52E cells were detected by subtraction PCR and microarray techniques. Genes found to be down regulated (0.17 / 0.31-times) were cytochrome c oxidase subunit I, BAR (an apoptosis regulator), heat-shock protein 70-like protein, and three proteins belonging to the translation machinery (ribosomal proteins S7 and L17, and S1, a member of the elongation factor 1-alpha family). The only up-regulated gene was glutathione Stransferase subunit 3A (1.89-times). Guided by the expression levels of these genes, it may be possible to improve renoprotective treatments during anti-neoplastic therapies.
ISSN:0960-3271
1477-0903
DOI:10.1191/0960327103ht393oa