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

• Published in: European journal of pharmacology 2003-12, Vol.482 (1), p.271-280
• Main Authors: Chatterjee, Prabal K., di Villa Bianca, Roberta D'Emmanuele, Sivarajah, Ahila, McDonald, Michelle C., Cuzzocrea, Salvatore, Thiemermann, Christoph
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Dithiocarbamates; Inducible nitric oxide synthase; Kidney - blood supply; Kidney - drug effects; Kidney - pathology; Male; Medical sciences; Nitric oxide; Nuclear factor-κB; Pharmacology. Drug treatments; Pyrrolidine dithiocarbamate; Pyrrolidines - pharmacology; Pyrrolidines - therapeutic use; Rats; Rats, Wistar; Renal/kidney; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; Reperfusion-injury; Thiocarbamates - pharmacology; Thiocarbamates - therapeutic use
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2003.09.071

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.