Stilbazulenyl nitrone decreases oxidative stress and reduces lung injury after hemorrhagic shock/resuscitation and LPS.
Antioxid Redox Signal
; 9(11): 1971-7, 2007 Nov.
Article
in En
| MEDLINE
| ID: mdl-17715998
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-kappaB-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-kappaB and generation of the pro-inflammatory cytokine TNF-alpha. Azulenyl nitrones such as STAZN represent a promising novel class of antioxidants for treating organ injury.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Resuscitation
/
Sesquiterpenes
/
Shock, Hemorrhagic
/
Lipopolysaccharides
/
Oxidative Stress
/
Lung
/
Lung Diseases
/
Antioxidants
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Antioxid Redox Signal
Journal subject:
METABOLISMO
Year:
2007
Document type:
Article
Affiliation country:
Canada