Pyrrolidine dithiocarbamate reduces renal dysfunction and injury caused by ischemia/reperfusion of the rat kidney.
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)-kappaB 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-kappaB 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.
Chatterjee
Prabal K
PK
Department of Experimental Medicine, Nephrology and Critical Care, William Harvey Research Institute, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK.
di Villa Bianca
Roberta D'Emmanuele
RD
Sivarajah
Ahila
A
McDonald
Michelle C
MC
Cuzzocrea
Salvatore
S
Thiemermann
Christoph
C
D000818:Animals; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013859:Thiocarbamates / Q000494:pharmacology / Q000627:therapeutic use*
D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid