Differential Activation of Signaling Pathways Involved in Cell Death, Survival and Inflammation by Radiocontrast Media in Human Renal Proximal Tubular Cells

• DOI: 10.1093/toxsci/kfq332
• Publication Date: 2010-10-29T22:45:48Z
• Authors: M. Andreucci; G. Lucisano; T. Faga; B. Bertucci; O. Tamburrini; A. Pisani; M. Sabbatini; S. Salzano; M. Vitale; G. Fuiano; A. Michael
• Keywords: Viability assay

Radiocontrast media (RCM) are widely used in clinical medicine but may lead to radiocontrast-induced nephropathy (RCIN). The pathogenesis of acute renal failure secondary RCM is not fully understood, direct toxic effects believed be a major cause RCIN. We have investigated the effect different types on signaling pathways known play role cell death, survival, and inflammation. HK-2 cells were incubated with sodium diatrizoate iomeprol (IOM) at concentration 75 mg I/ml for 2 h. Both caused an increase phosphorylation p38 mitogen-activated protein kinase (MAPK) (p38) c-Jun N-terminal kinases (JNKs) NF-κB (at Ser 276), having more drastic effect. Although viability was reduced significantly by both RCM, pretreated IOM recovered over 22-h time period after removal RCM. However, diatrizoate-treated rose 5 h then fell 22 decrease corresponded JNKs, p38, Akt, signal transducer activator transcription 3, forkhead box O3a, as well poly (ADP-ribose) polymerase caspase-3 cleavage. recovery IOM-treated most notably STAT3 induction Pim-1 kinase. There also interleukin-8 release indicating possibility proinflammatory A knowledge which exert their cytotoxic actions help finding future therapies