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In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis.
- Source :
-
Cell death & disease [Cell Death Dis] 2011 May 12; Vol. 2, pp. e155. Date of Electronic Publication: 2011 May 12. - Publication Year :
- 2011
-
Abstract
- Contrast-induced nephropathy accounts for >10% of all causes of hospital-acquired renal failure, causes a prolonged in-hospital stay and represents a powerful predictor of poor early and late outcome. Mechanisms of contrast-induced nephropathy are not completely understood. In vitro data suggests that contrast media (CM) induces a direct toxic effect on renal tubular cells through the activation of the intrinsic apoptotic pathway. It is unclear whether this effect has a role in the clinical setting. In this work, we evaluated the effects of CM both in vivo and in vitro. By analyzing urine samples obtained from patients who experienced contrast-induced acute kidney injury (CI-AKI), we verified, by western blot and immunohistochemistry, that CM induces tubular renal cells apoptosis. Furthermore, in cultured cells, CM caused a dose-response increase in reactive oxygen species (ROS) production, which triggered Jun N-terminal kinases (JNK1/2) and p38 stress kinases marked activation and thus apoptosis. Inhibition of JNK1/2 and p38 by different approaches (i.e. pharmacological antagonists and transfection of kinase-death mutants of the upstream p38 and JNK kinases) prevented CM-induced apoptosis. Interestingly, N-acetylcysteine inhibited ROS production, and thus stress kinases and apoptosis activation. Therefore, we conclude that CM-induced tubular renal cells apoptosis represents a key mechanism of CI-AKI.
- Subjects :
- Acute Kidney Injury chemically induced
Adult
Aged
Aged, 80 and over
Caspase 3 metabolism
Cells, Cultured
Enzyme Assays
Female
Humans
JNK Mitogen-Activated Protein Kinases metabolism
Kidney Tubules drug effects
Male
Middle Aged
Reactive Oxygen Species metabolism
bcl-2 Homologous Antagonist-Killer Protein metabolism
Acute Kidney Injury pathology
Apoptosis drug effects
Contrast Media adverse effects
Kidney Tubules pathology
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 2
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 21562587
- Full Text :
- https://doi.org/10.1038/cddis.2011.38