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IN VIVO DETECTION OF FREE RADICALS IN MOUSE SEPTIC ENCEPHALOPATHY USING MOLECULAR MRI AND IMMUNO-SPIN TRAPPING
Towner, Rheal A. et al. | Data do documento: 2013
Autor(es)
Towner, Rheal A.
Garteiser, Philippe
Bozza, Fernando A.
Smith, Nataliya
Saunders, Debra
d`Avila, Joana C. P.
Magno, Flora
Oliveira, Marcus F.
Ehrenshaft, Marilyn
Lupu, Florea
Silasi-Mansat, Robert
Ramirez, Dario C.
Gomez-Mejiba, Sandra E.
Mason, Ronald P.
Faria Neto, Hugo C. Castro
Afiliação
Oklahoma Medical Research Foundation. Advanced Magnetic Resonance Center. Oklahoma City, OK, USA.
Oklahoma Medical Research Foundation. Advanced Magnetic Resonance Center. Oklahoma City, OK, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Oklahoma Medical Research Foundation. Advanced Magnetic Resonance Center. Oklahoma City, OK, USA.
Oklahoma Medical Research Foundation. Advanced Magnetic Resonance Center. Oklahoma City, OK, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Laboratório de Bioquímica de Resposta ao Estresse. Rio de Janeiro, RJ, Brasil.
National Institute of Environmental Health Science. Laboratory of Pharmacology and Chemistry. ResearchTrianglePark, NC, USA.
Oklahoma Medical Research Foundation. Cardiovascular Biology. Oklahoma City, OK, USA.
Oklahoma Medical Research Foundation. Cardiovascular Biology. Oklahoma City, OK, USA.
National University of San Luis. Instituto Multidisciplinario de Investigaciones Biologicas–San Luis,CONICET. Laboratory of Experimental Medicine & Therapeutics. San Luis, Argentina.
National University of San Luis. Instituto Multidisciplinario de Investigaciones Biologicas–San Luis,CONICET. Laboratory of Experimental Medicine & Therapeutics. San Luis, Argentina
National Institute of Environmental Health Science. Laboratory of Pharmacology and Chemistry. ResearchTrianglePark, NC, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Resumo em Inglês
Free radicals are known to play a major role in sepsis. Combined immuno-spin trapping and molecular magnetic resonance imaging (MRI) was used to detect in vivo and in situ levels of free radicals in murine septic encephalopathy after cecal ligation and puncture (CLP). DMPO (5,5-dimethyl pyrroline N-oxide) was injected over 6 h after CLP, before administration of an anti-DMPO probe (anti-DMPO antibody bound to albumin–gadolinium–diethylene triamine pentaacetic acid–biotin MRI targeting contrast agent). In vitro assessment of the anti-DMPO probe in oxidatively stressed mouse astrocytes significantly decreased T1 relaxation (p < 0.0001) compared to controls. MRI detected the presence of anti-DMPO adducts via a substantial decrease in %T1 change within the hippocampus, striatum, occipital, and medial cortex brain regions (p < 0.01 for all) in septic animals compared to shams, which was sustained for over 60 min (p < 0.05 for all). Fluorescently labeled streptavidin was used to target the anti-DMPO probe biotin, which was elevated in septic brain, liver, and lungs compared to sham. Ex vivo DMPO adducts (qualitative) and oxidative products, including 4-hydroxynonenal and 3-nitrotyrosine (quantitative, p < 0.05 for both), were elevated in septic brains compared to shams. This is the first study that has reported on the detection of in vivo and in situ levels of free radicals in murine septic encephalopathy.
Palavras-chave em inglês
Immuno-spin trapping
Free radicals
Molecular MRI
Sepsis
Cecal ligation and puncture
Mice
in vivo
DMPO
Fluorescence microscopy
4-Hydroxynonenal
3-Nitrotyrosine
 
DeCS
Radicais Livres
Sepse
Microscopia de Fluorescência
Camundongos
 
Editor
Elsevier
Referência
TOWNER, Rheal A. et al. In vivo detection of free radicals in mouse septic encephalopathy using molecular MRI and immuno-spin trapping. Free Radical Biology and Medicine, v.65, p.828–837, 2013.
ISSN
0891-5849
10.1016/j.freeradbiomed.2013.08.172