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09.11.2017 | ORIGINAL ARTICLE

Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats

verfasst von: Amanda Della Giustina, Sandra Bonfante, Graciela Freitas Zarbato, Lucinéia Gainski Danielski, Khiany Mathias, Aloir Neri de Oliveira Jr, Leandro Garbossa, Taise Cardoso, Maria Eduarda Fileti, Raquel Jaconi De Carli, Mariana Pereira Goldim, Tatiana Barichello, Fabricia Petronilho

Erschienen in: Inflammation | Ausgabe 1/2018

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Abstract

Sepsis is defined as life-threatening organ dysfunction induced by a disrupted host response to infecting pathogens. Evidences suggest that oxidative stress is intrinsically related to sepsis progression. Dimethyl fumarate (DMF) is a novel oral therapeutic agent with anti-oxidant properties which exerts protective effects through activation of nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2). Thus, the aim of this study is to evaluate the effect of DMF in different organs of rats submitted to an animal model of sepsis. Adult male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP) procedure and sham-operated rats was considered control group. The experimental groups were divided into sham + vehicle, sham + DMF, sham + NAC, CLP + vehicle, CLP + DMF, and CLP + NAC. Rats were treated by oral gavage with DMF immediately after and 12 h after surgery, or NAC (s.c.) at 3, 6, and 12 h after surgery. Twenty-four hours after sepsis induction, neutrophil infiltration, nitrite/nitrate concentrations, oxidative damage to lipids and proteins, superoxide dismutase (SOD), and catalase (CAT) activities were evaluated in the heart, liver, lung, and kidney. Septic animals presented increased neutrophil infiltration, NO metabolism, oxidative damage to lipids and proteins, and decreases of SOD and CAT activities, mainly in the heart, liver, and lung, while DMF-treated animals showed significant reduction in neutrophil infiltration, NO metabolism, and oxidative damage followed by increased SOD and CAT activities. DMF is effective in preventing oxidative stress and inflammation in rats 24 h after sepsis induction.

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Titel: Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats
verfasst von: Amanda Della Giustina
Sandra Bonfante
Graciela Freitas Zarbato
Lucinéia Gainski Danielski
Khiany Mathias
Aloir Neri de Oliveira Jr
Leandro Garbossa
Taise Cardoso
Maria Eduarda Fileti
Raquel Jaconi De Carli
Mariana Pereira Goldim
Tatiana Barichello
Fabricia Petronilho
Publikationsdatum: 09.11.2017
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 1/2018
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-017-0689-z

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