Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, University of South Santa Catarina, Tubarao, SC, Brazil.
Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Inflammation. 2018 Feb;41(1):315-327. doi: 10.1007/s10753-017-0689-z.
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.
脓毒症是指宿主对感染病原体的反应失调导致危及生命的器官功能障碍。有证据表明，氧化应激与脓毒症的进展有内在关系。富马酸二甲酯（DMF）是一种新型口服治疗药物，具有抗氧化特性，通过激活核因子红细胞 2（NFE2）相关因子 2（Nrf2）发挥保护作用。因此，本研究旨在评估 DMF 在接受脓毒症动物模型的大鼠不同器官中的作用。成年雄性 Wistar 大鼠通过盲肠结扎和穿刺（CLP）程序进行脓毒症，假手术大鼠被认为是对照组。实验组分为假手术+载体、假手术+DMF、假手术+NAC、CLP+载体、CLP+DMF 和 CLP+NAC。大鼠在手术后立即和 12 小时通过口服灌胃给予 DMF，或在手术后 3、6 和 12 小时通过皮下给予 NAC。在脓毒症诱导 24 小时后，评估心脏、肝脏、肺和肾脏中的中性粒细胞浸润、亚硝酸盐/硝酸盐浓度、脂质和蛋白质的氧化损伤、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性。脓毒症动物表现出中性粒细胞浸润增加、NO 代谢增加、脂质和蛋白质氧化损伤增加，以及 SOD 和 CAT 活性降低，主要在心脏、肝脏和肺部，而 DMF 治疗的动物表现出中性粒细胞浸润、NO 代谢和氧化损伤显著减少，随后 SOD 和 CAT 活性增加。DMF 可有效预防脓毒症诱导后 24 小时大鼠的氧化应激和炎症。
