Differential activation of signaling pathways involved in cell death, survival and inflammation by radiocontrast media in human renal proximal tubular cells.
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| Abstract |
Radiocontrast media (RCM) are widely used in clinical medicine but may lead to radiocontrast-induced nephropathy (RCIN). The pathogenesis of acute renal failure secondary to RCM is not fully understood, but direct toxic effects are believed to be a major cause of RCIN. We have investigated the effect of different types of RCM on signaling pathways known to play a role in cell death, survival, and inflammation. HK-2 cells were incubated with sodium diatrizoate and iomeprol (IOM) at a concentration of 75 mg I/ml for 2 h. Both RCM caused an increase in phosphorylation of p38 mitogen-activated protein kinase (MAPK) (p38) and c-Jun N-terminal kinases (JNKs) and NF-κB (at Ser 276), with sodium diatrizoate having a more drastic effect. Although cell viability was reduced significantly by both RCM, in cells pretreated with IOM the cell viability recovered over a 22-h time period after removal of the RCM. However, viability of diatrizoate-treated cells rose at 5 h but then fell at 22 h after removal of the RCM. The decrease in cell viability in diatrizoate-treated cells corresponded with an increase in phosphorylation of JNKs, p38, and NF-κB and a decrease in phosphorylation of Akt, signal transducer and activator of transcription 3, and forkhead box O3a, as well as poly (ADP-ribose) polymerase and caspase-3 cleavage. The recovery in viability of IOM-treated cells corresponded most notably with an increase in STAT3 phosphorylation and induction of Pim-1 kinase. There was also an increase in interleukin-8 release by diatrizoate-treated cells indicating the possibility of proinflammatory effects of RCM. A knowledge of the signaling pathways by which RCM exert their cytotoxic actions may help in finding future therapies for RCIN.
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| Authors | Michele Andreucci, Gaetano Lucisano, Teresa Faga, Bernardo Bertucci, Oscar Tamburrini, Antonio Pisani, Massimo Sabbatini, Salvatore Salzano, Mario Vitale, Giorgio Fuiano, Ashour Michael |
| Journal | Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 119 Issue 2 Pg. 408-16 (Feb 2011) ISSN: 1096-0929 [Electronic] United States |
| PMID | 21036957 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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