IMIBIO-SL   20937
INSTITUTO MULTIDISCIPLINARIO DE INVESTIGACIONES BIOLOGICAS DE SAN LUIS
Unidad Ejecutora - UE
artículos
Título:
THE SPIN TRAP 5,5-DIMETHYL-1-PYRROLINE N-OXIDE INHIBITS LIPOPOLYSACCHARIDE-INDUCED INFLAMMATION IN RAW264.7 CELLS
Autor/es:
ZILI, ZHAI; SANDRA E. GOMEZ-MEJIBA; HUA, ZHU; FLOREA, LUPU; DARIO C. RAMIREZ
Revista:
LIFE SCIENCES
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2012 vol. 90 p. 432 - 439
ISSN:
0024-3205
Resumen:
AIM:
Exposure of macrophages to lipopolysaccharide (LPS)
induces oxidative and inflammatory stresses, which cause cell damage.
Antioxidant and anti-inflammatory properties have been attributed to the
nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), commonly
used in free radical analysis, but these aspects of DMPO have been
little explored. In this study, we sought to establish the
anti-inflammatory activity of DMPO, presumably by removing free radicals
which otherwise help activate inflammatory response and damage cells.
MAIN METHODS:
RAW
264.7 macrophages were treated with LPS and/or DMPO for different time
points, cell damage, production of inflammatory mediators, inducible
nitric oxide synthase (iNOS) expression, NF-κB p65 activation,
phosphorylation of MAPKs and Akt, and intracellular reactive oxygen
species (ROS) were determined.
KEY FINDINGS:
After cells
were treated with LPS and/or DMPO for 24 h, DMPO reduced the LPS-induced
inflammatory response as indicated by downregulated iNOS expression and
production of inflammatory mediators. Accordingly, DMPO protected cells
from LPS-induced cytotoxicity. In order to understand the mechanistic
basis of these DMPO effects, the NF-κB p65 activation and the
phosphorylation of MAPKs and Akt were examined. We found, by assaying
cells treated with LPS and/or DMPO for 15-60 min, that DMPO inhibited
the phosphorylation of MAPKs, Akt, and IκBα, and reduced the NF-κB p65
translocation. Furthermore, we demonstrated that DMPO inhibited
LPS-induced ROS production.
SIGNIFICANCE:
DMPO showed the
anti-inflammatory activity and attenuated LPS-induced cell damage, most
likely by reducing ROS production and thus preventing the subsequent
inflammatory activation and damage.