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Exogenous nitric oxide can control SIRS and downregulate NFkappaB.

Francisco S Lozano·Marcello B Barros·Francisco J García-Criado·Alberto Gomez-Alonso
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Abstract

BACKGROUND: Nitric oxide (NO) participates in inflammation and affects almost all steps of its development. Several experimental studies have unveiled the beneficial effects of NO through modulation of the Systemic Inflammatory Response Syndrome (SIRS). In this sense, in the present work we attempted to evaluate the beneficial effects of exogenous NO and its levels of action (biochemical and cellular) in a model of SIRS induced by two sequential insults. MATERIALS AND METHODS: Dacron graft implantation (first insult) and subsequent administration of Zymosan A (second insult) in Wistar rats. The animals were divided into four groups: 1) No manipulation (Basal); 2) Laparotomy (L) + mineral oil (Sham); 3) L + Graft-Zymosan (GZ) (Control); and 4) L + GZ + NO (Assay). Determinations: Survival, TNF-alpha, SOA, ICAM-1, and NFkappaB. RESULTS: The model established (Control) induced a mortality rate of 20%. Also, it significantly increased the levels of TNF-alpha (P <0.001) and SOA (P <0.01), ICAM-1 expression, and NFkappaB levels (P <0.05). Treatment with NO reduced mortality to 0%, significantly decreasing TNF-alpha (P <0.001) and SOA (P <0.01) levels, ICAM-1 expression, and NFkappaB levels (P <0.05). CONCLUSION: The exogenous administration of NO before the two sequential insults controlled SIRS at biochemical level (TNF-alpha, SOA) and at cellular level (transcription) in a lasting manner. The cascade-like interrelationship of both levels and the study design do not allow us the pinpoint the key to its modulation.

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AnimalsAnti-Inflammatory Agents, Non-SteroidalBiocompatible MaterialsBiomarkersBlood Vessel Prosthesis ImplantationDown-RegulationIntercellular Adhesion Molecule-1MaleModels, AnimalNF-kappa BNitric OxidePolyethylene TerephthalatesRatsRats, WistarSingle-Blind MethodSystemic Inflammatory Response SyndromeZymosanbeta-GlucansEvaluation StudyJournal ArticleResearch Support, Non-U.S. Gov't

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Francisco S Lozano, Marcello B Barros, Francisco J García-Criado, Alberto Gomez-Alonso. 2005. Exogenous nitric oxide can control SIRS and downregulate NFkappaB.. https://doi.org/10.1016/j.jss.2004.08.029

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