TY - JOUR
T1 - Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats
AU - Giustina, Amanda Della
AU - Bonfante, Sandra
AU - Zarbato, Graciela Freitas
AU - Danielski, Lucinéia Gainski
AU - Mathias, Khiany
AU - de Oliveira, Aloir Neri
AU - Garbossa, Leandro
AU - Cardoso, Taise
AU - Fileti, Maria Eduarda
AU - De Carli, Raquel Jaconi
AU - Goldim, Mariana Pereira
AU - Barichello, Tatiana
AU - Petronilho, Fabricia
N1 - Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - inflammation
KW - organ injury
KW - oxidative stress
KW - sepsis
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UR - http://www.scopus.com/inward/citedby.url?scp=85033432118&partnerID=8YFLogxK
U2 - 10.1007/s10753-017-0689-z
DO - 10.1007/s10753-017-0689-z
M3 - Article
C2 - 29124567
AN - SCOPUS:85033432118
SN - 0360-3997
VL - 41
SP - 315
EP - 327
JO - Inflammation
JF - Inflammation
IS - 1
ER -