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

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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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Acknowledgments

This research was supported by grants from CNPq and CAPES (FP). FP and TB are CNPq research fellows. The funding sources had no involvement in the conduction of the research, preparation of the article, or in the decision to submit the article for publication.

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Authors and Affiliations

  1. Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, University of South Santa Catarina, Tubarao, SC, Brazil

    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 & Fabricia Petronilho

  2. Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil

    Tatiana Barichello

  3. Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Tatiana Barichello

  4. Laboratório de Neurobiologia de Processos Inflamatórios e Metabólicos, Programa de Pós-graduação em Ciências da Saúde, Universidade do Sul de Santa Catarina, Tubarão, SC, Brazil

    Fabricia Petronilho

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  1. Amanda Della Giustina
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Correspondence to Fabricia Petronilho.

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All studies were performed in compliance with the National Institutes of Health Guidelines and with the approval of the Animal Care and Experimentation Committee of UNISUL (protocol number 13.026.4.03.IV), Brazil.

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Giustina, A.D., Bonfante, S., Zarbato, G.F. et al. Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats. Inflammation 41, 315–327 (2018). https://doi.org/10.1007/s10753-017-0689-z

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