Pyrrolidine dithiocarbamate reduces renal dysfunction and injury caused by ischemia/reperfusion of the rat kidney

P.K. Chatterjee, R.D.D. Bianca, A. Sivarajah, M.C. McDonald, S. Cuzzocrea, C. Thiemermann

Research output: Contribution to journalArticle

Abstract

Dithiocarbamates can modulate the expression of genes associated with inflammation or development of ischemia/reperfusion injury. Here, we investigate the effects of pyrrolidine dithiocarbamate, an inhibitor of nuclear factor (NF)-κB activation, on the renal dysfunction and injury caused by ischemia/reperfusion of the rat kidney. Bilateral clamping of renal pedicles (45 min) followed by reperfusion (6 h) caused significant renal dysfunction and marked renal injury. Pyrrolidine dithiocarbamate (100 mg/kg, administered i.v.) significantly reduced biochemical and histological evidence of renal dysfunction and injury caused by ischemia/reperfusion of the rat kidney. Furthermore, pyrrolidine dithiocarbamate markedly reduced the expression of inducible nitric oxide synthase (iNOS) protein and significantly reduced serum levels of nitric oxide. Finally, pyrrolidine dithiocarbamate inhibited the activation of NF-κB by preventing its translocation from the cytoplasm into the nuclei of renal cells. These results demonstrate that pyrrolidine dithiocarbamate reduces renal ischemia/reperfusion injury and that dithiocarbamates may provide beneficial actions against ischemic acute renal failure.
Original languageEnglish
Pages (from-to)271-280
Number of pages10
JournalEuropean Journal of Pharmacology
Volume482
Issue number1-3
Publication statusPublished - Dec 2003

Keywords

  • Renal/kidney
  • reperfusion-injury
  • Dithiocarbamates
  • Pyrrolidine dithiocarbamate
  • Nuclear factor-κB
  • inducible nitric oxide synthase
  • Nitric oxide

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    Chatterjee, P. K., Bianca, R. D. D., Sivarajah, A., McDonald, M. C., Cuzzocrea, S., & Thiemermann, C. (2003). Pyrrolidine dithiocarbamate reduces renal dysfunction and injury caused by ischemia/reperfusion of the rat kidney. European Journal of Pharmacology, 482(1-3), 271-280.