Pyrrolidine dithiocarbamate reduces lung reperfusion injury

Stewart M. Long, Victor E. Laubach, Curtis G. Tribble, Aditya K. Kaza, Steven M. Fiser, David C. Cassada, John A. Kern, Irving L. Kron

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background. The inflammatory cascade has emerged as the primary mediator of reperfusion injury. Nuclear factor κB (NF-κB) is a rapid response transcription factor that activates genes responsible for the mediators of inflammation. Heat shock protein 70 (HSP70) has been shown to protect against lung injury. We hypothesized that the antioxidant pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB and upregulator of HSP70, would decrease lung injury after ischemia and reperfusion. Methods. Using our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 10-h storage (4°C) and blood reperfusion for 30 min. Group I lungs (n = 5) served as controls. In group II lungs (n = 5), both lung and blood donors received PDTC (100 mg/kg) intravenously 30 min before harvest. NF-κB activity was evaluated with electrophoretic mobility shift assay, and Western blot was performed for HSP70. Results. Group II demonstrated superior pulmonary function. Although HSP70 expression was somewhat elevated in group II lungs, NF-κB binding activity was not different between the groups. Conclusions. PDTC improves pulmonary function after ischemia and reperfusion in an isolated rabbit lung model. The improved function correlates with elevated HSP70 expression during initial reperfusion, independent of NF-κB activity.

Original languageEnglish (US)
Pages (from-to)12-18
Number of pages7
JournalJournal of Surgical Research
Volume112
Issue number1
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

Keywords

  • HSP70
  • Inflammation
  • Ischemia
  • Lung
  • NF-κB
  • Pulmonary
  • Reperfusion injury
  • Transplant

ASJC Scopus subject areas

  • Surgery

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  • Cite this

    Long, S. M., Laubach, V. E., Tribble, C. G., Kaza, A. K., Fiser, S. M., Cassada, D. C., Kern, J. A., & Kron, I. L. (2003). Pyrrolidine dithiocarbamate reduces lung reperfusion injury. Journal of Surgical Research, 112(1), 12-18. https://doi.org/10.1016/S0022-4804(03)00139-2