Stilbazulenyl nitrone decreases oxidative stress and reduces lung injury after hemorrhagic shock/resuscitation and LPS

P. S. Tawadros, K. A. Powers, I. Yang, D. A. Becker, M. D. Ginsberg, K. Szaszi, A. Kapus, O. D. Rotstein

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Multiorgan failure is a major cause of late morbidity and mortality after trauma. Reactive oxygen species generated during shock/resuscitation contribute to tissue injury by priming the immune system for an exaggerated response to subsequent inflammatory stimuli such as LPS. Stilbazulenyl nitrone (STAZN) is a novel second-generation azulenyl nitrone that has been shown to have potent antioxidant properties in a rat model of brain ischemia. We hypothesized that STAZN may confer protection against lung injury after shock/resuscitation and LPS by reducing oxidative stress and lowering the production of NF-κB-dependent pro-inflammatory cytokines. Sprague-Dawley rats were submitted to a two-hit model of lung injury involving hemorrhagic shock/resuscitation and subsequent intratracheal LPS injection, with and without intraperitoneal injections of STAZN. STAZN reduced overall lung injury in response to LPS alone and also after shock/resuscitation plus LPS. STAZN also reduced plasma levels of 8-isoprostane, a proxy measure of oxidative stress, indicating its antioxidant activity in vivo. The effect of STAZN was, at least in part, related to its effect on nuclear translocation of NF-κB and generation of the pro-inflammatory cytokine TNF-α. Azulenyl nitrones such as STAZN represent a promising novel class of antioxidants for treating organ injury.

Original languageEnglish (US)
Pages (from-to)1971-1977
Number of pages7
JournalAntioxidants and Redox Signaling
Volume9
Issue number11
DOIs
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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