In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis

C. Quintavalle, M. Brenca, F. De Micco, D. Fiore, S. Romano, M. F. Romano, F. Apone, A. Bianco, M. A. Zabatta, G. Troncone, C. Briguori, G. Condorelli

Research output: Contribution to journalArticlepeer-review

Abstract

Contrast-induced nephropathy accounts for >10% of all causes of hospital-acquired renal failure, causes a prolonged inhospital 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 kinasedeath 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.

Original languageEnglish
Article numbere155
JournalCell Death and Disease
Volume2
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • Apoptosis
  • Contrast media
  • Kidney
  • Prevention

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience
  • Medicine(all)

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