Top

Published in:

01-02-2018 | ORIGINAL ARTICLE

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

Authors: 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

Published in: Inflammation | Issue 1/2018

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.

Singer, Mervyn, D.S. Deutschman, C.W. Seymour, M. Shankar-Hari, D. Annane, M. Bauer, R. Bellomo, and G.R. Bernard. 2016. The third international consensus definitions for sepsis and septic shock (sepsis-3). The Journal of the American Medical Association 315: 801–810. https://doi.org/10.1001/jama.2016.0287.The.CrossRefPubMed

Van der Poll, Tom. 2016. Future of sepsis therapies. Critical Care 20: 106. https://doi.org/10.1186/s13054-016-1274-9.CrossRefPubMedPubMedCentral

Morin, Emily E., L. Guo, A. Schwendeman, and X.A. Li. 2015. HDL in sepsis—risk factor and therapeutic approach. Frontiers in Pharmacology 6: 1–9. https://doi.org/10.3389/fphar.2015.00244.CrossRef

Petronilho, Fabricia, D. Florentino, L.G. Danielski, L.C. Vieira, M.M. Martins, A. Vieira, S. Bonfante, M.P. Goldim, and F. Vuolo. 2015. Alpha-lipoic acid attenuates oxidative damage in organs after sepsis. Inflammation 39: 357–365. https://doi.org/10.1007/s10753-015-0256-4.CrossRef

Polat, Gizem, R.A. Ugan, E. Cadirci, and Z. Halici. 2017. Sepsis and septic shock: current treatment strategies and new approaches. The Eurasian Journal of Medicine 49: 53–58. https://doi.org/10.5152/eurasianjmed.2017.17062.CrossRefPubMedPubMedCentral

Bone, R.C. 1991. Gram-negative sepsis. Background, clinical features, and intervention. Chest 100: 802–808.CrossRefPubMed

Hattori, Yuichi, K. Hattori, T. Suzuki, and N. Matsuda. 2017. Recent advances in the pathophysiology and molecular basis of sepsis-associated organ dysfunction: novel therapeutic implications and challenges. Pharmacology & Therapeutics. https://doi.org/10.1016/j.pharmthera.2017.02.040.

Andrades, Michael Everton, C. Ritter, and F. Dal-Pizzol. 2009. The role of free radicals in sepsis development. Frontiers in Bioscience 1: 277–287.

Barichello, Tatiana, J.J. Fortunato, A.M. Vitali, G. Feier, A. Reinke, J.C.F. Moreira, J. Quevedo, and F. Dal-Pizzol. 2006. Oxidative variables in the rat brain after sepsis induced by cecal ligation and perforation. Critical Care Medicine 34: 886–889. https://doi.org/10.1097/01.CCM.0000201880.50116.12.CrossRefPubMed

10.

Victor, Victor M., M. Rocha, J.V. Esplugues, and M. De la Fuente. 2005. Role of free radicals in sepsis: antioxidant therapy. Current Pharmaceutical Design 11: 3141–3158.CrossRefPubMed

11.

Hotchkiss, Richard S., and I.E. Karl. 2003. The pathophysiology and treatment of sepsis. The New England Journal of Medicine 348: 138–150. https://doi.org/10.1056/NEJMra021333.CrossRefPubMed

12.

Ritter, Cristiane, M. Andrades, M.L.C. Frota, F. Bonatto, R.A. Pinho, M. Polydoro, F. Klamt, et al. 2003. Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation. Intensive Care Medicine 29: 1782–1789. https://doi.org/10.1007/s00134-003-1789-9.CrossRefPubMed

13.

Andrades, Michael, C. Ritter, J.C.F. Moreira, and F. Dal-Pizzol. 2005. Oxidative parameters differences during non-lethal and lethal sepsis development. Journal of Surgical Research 125: 68–72. https://doi.org/10.1016/j.jss.2004.11.008.CrossRefPubMed

14.

Andrades, Michael, C. Ritter, M.R. De Oliveira, E.L. Streck, J.C. Fonseca Moreira, and F. Dal-Pizzol. 2011. Antioxidant treatment reverses organ failure in rat model of sepsis: role of antioxidant enzymes imbalance, neutrophil infiltration, and oxidative stress. Journal of Surgical Research 167: e307–e313. https://doi.org/10.1016/j.jss.2009.08.005.CrossRefPubMed

15.

Ritter, Cristiane, M.E. Andrades, A. Reinke, S. Menna-Barreto, J.C.F. Moreira, and F. Dal-Pizzol. 2004. Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Critical Care Medicine 32: 342–349. https://doi.org/10.1097/01.CCM.0000109454.13145.CA.CrossRefPubMed

16.

Albrecht, Philipp, I. Bouchachia, C. Zimmermann, H.H. Hofstetter, Z. Kovacs, N. Henke, D. Lisak, et al. 2012. Effects of dimethyl fumarate on neuroprotection and immunomodulation. Journal of Neuroinflammation 9: 163. https://doi.org/10.1186/1742-2094-9-163.CrossRefPubMedPubMedCentral

17.

Parodi, Benedetta, C. Cordano, S. Morando, A. Bragoni, D. Giunti, C. Usai, D. Centonze, N.K. De Rosbo, R.H. Scannevin, and A. Uccelli. 2014. Monomethyl fumarate inhibits the NFkB pathway and pro-inflammatory cytokine expression in microglia through HCA2 signaling via the AMPK/Sirt axis. Journal of Neuroimmunology 275: 167–168. https://doi.org/10.1016/j.jneuroim.2014.08.450.CrossRef

18.

Werdenberg, D., R. Joshi, S. Wolffram, H.P. Merkle, and P. Langguth. 2003. Presystemic metabolism and intestinal absorption of antipsoriatic fumaric acid esters. Biopharmaceutics & Drug Disposition 24: 259–273. https://doi.org/10.1002/bdd.364.CrossRef

19.

Litjens, N.H.R., J. Burggraaf, E. Van Strijen, C. Van Gulpen, H. Mattie, R.C. Schoemaker, J.T. Van Dissel, H.B. Thio, and P.H. Nibbering. 2004. Pharmacokinetics of oral fumarates in healthy subjects. British Journal of Clinical Pharmacology 58: 429–432. https://doi.org/10.1111/j.1365-2125.2004.02145.x.CrossRefPubMedPubMedCentral

20.

Ma, Qiang. 2013. Role of Nrf2 in oxidative stress and toxicity. Annual Review of Pharmacology and Toxicology 53: 401–426. https://doi.org/10.1146/annurev-pharmtox-011112-140320.CrossRefPubMedPubMedCentral

21.

Linker, R.A., D.H. Lee, S. Ryan, A.M. Van Dam, R. Conrad, P. Bista, W. Zeng, et al. 2011. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 134: 678–692. https://doi.org/10.1093/brain/awq386.CrossRefPubMed

22.

Jing, X., H. Shi, C. Zhang, M. Ren, M. Han, X. Wei, X. Zhang, and H. Lou. 2015. Dimethyl fumarate attenuates 6-OHDA-induced neurotoxicity in SH-SY5Y cells and in animal model of Parkinson’s disease by enhancing Nrf2 activity. Neuroscience 286: 131–140. https://doi.org/10.1016/j.neuroscience.2014.11.047.CrossRefPubMed

23.

Wilms, Henrik, J. Sievers, U. Rickert, M. Rostami-Yazdi, U. Mrowietz, and R. Lucius. 2010. Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1beta, TNF-alpha and IL-6 in an in-vitro model of brain inflammation. Journal of Neuroinflammation 7: 30. https://doi.org/10.1186/1742-2094-7-30.CrossRefPubMedPubMedCentral

24.

Scannevin, R.H., S. Chollate, M.-Y. Jung, M. Shackett, H. Patel, P. Bista, W. Zeng, et al. 2012. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway. Journal of Pharmacology and Experimental Therapeutics 341: 274–284. https://doi.org/10.1124/jpet.111.190132.CrossRefPubMed

25.

Wierinckx, Anne, J. Brevé, D. Mercier, M. Schultzberg, B. Drukarch, and A.M. Van Dam. 2005. Detoxication enzyme inducers modify cytokine production in rat mixed glial cells. Journal of Neuroimmunology 166: 132–143. https://doi.org/10.1016/j.jneuroim.2005.05.013.CrossRefPubMed

26.

Fink, M.P., and S.O. Heard. 1990. Laboratory models of sepsis and septic shock. The Journal of Surgical Research 49: 186–196.CrossRefPubMed

27.

Carvalho, Dickson, F. Petronilho, F. Vuolo, R.A. Machado, L. Constantino, R. Guerrini, G. Calo, E.C. Gavioli, E.L. Streck, and F. Dal-Pizzol. 2008. The nociceptin/orphanin FQ-NOP receptor antagonist effects on an animal model of sepsis. Intensive Care Medicine 34: 2284–2290. https://doi.org/10.1007/s00134-008-1313-3.CrossRefPubMed

28.

Reick, Christiane, G. Ellrichmann, J. Thone, R.H. Scannevin, C. Saft, R.A. Linker, and R. Gold. 2014. Neuroprotective dimethyl fumarate synergizes with immunomodulatory interferon beta to provide enhanced axon protection in autoimmune neuroinflammation. Experimental Neurology 257: 50–56. https://doi.org/10.1016/j.expneurol.2014.04.003.CrossRefPubMed

29.

Kramer, Tobias, Theresa Grob, Lutz Menzel, Tobias Hirnet, Eva Griemert, Konstantin Radyushkin, Serge C. Thal, Axel Methner, and Michael K.E. Schaefer. 2017. Dimethyl fumarate treatment after traumatic brain injury prevents depletion of antioxidative brain glutathione and confers neuroprotection. Journal of Neurochemistry. https://doi.org/10.1111/jnc.14220.

30.

Barichello, Tatiana, R.A. Machado, L. Constantino, S.S. Valvassori, G.Z. Réus, M.R. Martins, F. Petronilho, C. Ritter, J. Quevedo, and F. Dal-Pizzol. 2007. Antioxidant treatment prevented late memory impairment in an animal model of sepsis. Critical Care Medicine 35: 2186–2190. https://doi.org/10.1097/01.CCM.0000281452.60683.96.CrossRefPubMed

31.

Borgstrom, L., B. Kagedal, and O. Paulsen. 1986. Pharmacokinetics of N-acetylcysteine in man. European Journal of Clinical Pharmacology 31: 217–222.CrossRefPubMed

32.

De Young, L.M., J.B. Kheifets, S.J. Ballaron, and J.M. Young. 1989. Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents. Agents and Actions 26: 335–341.CrossRefPubMed

33.

Green, L.C., D.A. Wagner, J. Glogowski, P.L. Skipper, J.S. Wishnok, and S.R. Tannenbaum. 1982. Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids. Analytical Biochemistry 126: 131–138. https://doi.org/10.1016/0003-2697(82)90118-X.CrossRefPubMed

34.

Draper, H.H., and M. Hadley. 1990. Malondialdehyde determination as index of lipid peroxidation. Methods in Enzymology 186: 421–431.CrossRefPubMed

35.

Levine, R.L., D. Garland, C.N. Oliver, A. Amici, I. Climent, A.G. Lenz, B.W. Ahn, S. Shaltiel, and E.R. Stadtman. 1990. Determination of carbonyl content in oxidatively modified proteins. Methods in Enzymology 186: 464–478.CrossRefPubMed

36.

Bannister, J.V., and L. Calabrese. 1987. Assays for superoxide dismutase. Methods of Biochemical Analysis 32: 279–312.CrossRefPubMed

37.

Aebi, H. 1984. Catalase in vitro. Methods in Enzymology 105: 121–126.CrossRefPubMed

38.

Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. The Journal of Biological Chemistry 193: 265–275.PubMed

39.

Li, Cheng Chung, H.T. Yang, Y.C. Hou, Y.S. Chiu, and W.C. Chiu. 2014. Dietary fish oil reduces systemic inflammation and ameliorates sepsis-induced liver injury by up-regulating the peroxisome proliferator-activated receptor gamma-mediated pathway in septic mice. Journal of Nutritional Biochemistry 25: 19–25. https://doi.org/10.1016/j.jnutbio.2013.08.010.CrossRefPubMed

40.

Papayannopoulos, Venizelos, Kathleen D. Metzler, Abdul Hakkim, and Arturo Zychlinsky. 2010. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. The Journal of Cell Biology 191: 677–691. https://doi.org/10.1083/jcb.201006052.CrossRefPubMedPubMedCentral

41.

Mishra, Hemant K., J. Ma, and B. Walcheck. 2017. Ectodomain shedding by ADAM17: its role in neutrophil recruitment and the impairment of this process during sepsis. Frontiers in Cellular and Infection Microbiology 7: 138. https://doi.org/10.3389/fcimb.2017.00138.CrossRefPubMedPubMedCentral

42.

Shen, Xiao-Fei, K. Cao, J.-P. Jiang, W.-X. Guan, and J.-F. Du. 2017. Neutrophil dysregulation during sepsis: an overview and update. Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/jcmm.13112.

43.

Lerman, Yelena V., and M. Kim. 2015. Neutrophil migration under normal and sepsis conditions. Cardiovascular & Hematological Disorders Drug Targets 15: 19–28.CrossRef

44.

Müller, Susen, M. Behnen, K. Bieber, S. Möller, L. Hellberg, M. Witte, M. Hänsel, et al. 2016. Dimethylfumarate impairs neutrophil functions. Journal of Investigative Dermatology 136: 117–126. https://doi.org/10.1038/JID.2015.361.CrossRefPubMed

45.

Chen, Hui, J.C. Assmann, A. Krenz, M. Rahman, M. Grimm, C.M. Karsten, J. Kohl, S. Offermanns, N. Wettschureck, and M. Schwaninger. 2014. Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate’s protective effect in EAE. The Journal of Clinical Investigation 124: 2188–2192. https://doi.org/10.1172/JCI72151.CrossRefPubMedPubMedCentral

46.

Liu, Xiuting, W. Zhou, X. Zhang, P. Lu, Q. Du, L. Tao, Y. Ding, Y. Wang, and R. Hu. 2016. Dimethyl fumarate ameliorates dextran sulfate sodium-induced murine experimental colitis by activating Nrf2 and suppressing NLRP3 inflammasome activation. Biochemical Pharmacology 112: 37–49. https://doi.org/10.1016/j.bcp.2016.05.002.CrossRefPubMed

47.

Jobgen, Wenjuan S., S.C. Jobgen, H. Li, C.J. Meininger, and G. Wu. 2007. Analysis of nitrite and nitrate in biological samples using high-performance liquid chromatography. Journal of Chromatography B 851: 71–82. https://doi.org/10.1016/j.jchromb.2006.07.018.CrossRef

48.

Pfeilschifter, Josef, W. Eberhardt, and A. Huwiler. 2003. Nitric oxide and mechanisms of redox signaling. Journal of the American Society of Nephrology 14: S237–S240.CrossRefPubMed

49.

Stamler, Jonathan S. 1994. Redox signaling: nitrosylation and related target interactions of nitric oxide. Cell 78: 931–936. https://doi.org/10.1016/0092-8674(94)90269-0.CrossRefPubMed

50.

Lobo, Suzana M, Francisco G Soriano, Denise F Barbeiro, Daniel De Backer, Qinghua Sun, Zizhi Tu, George Dimopoulos, et al. 2009. Effects of dobutamine on gut mucosal nitric oxide production during endotoxic shock in rabbits. Medical Science Monitor 15. United States: BR37–42.

51.

Soriano, Francisco Garcia, C.B. Lorigados, P. Pacher, and C. Szabo. 2011. Effects of a potent peroxynitrite decomposition catalyst in murine models of endotoxemia and sepsis. Shock 35: 560–566. https://doi.org/10.1097/SHK.0b013e31820fe5d5.CrossRefPubMedPubMedCentral

52.

Lin, Shao Xia, L Lisi, C Dello Russo, P E Polak, A Sharp, G Weinberg, S Kalinin, and D L Feinstein. 2011. The anti-inflammatory effects of dimethyl fumarate in astrocytes involve glutathione and haem oxygenase-1. ASN Neuro 3. United States. https://doi.org/10.1042/AN20100033.

53.

Victor, Victor M., J.V. Espulgues, A. Hernandez-Mijares, and M. Rocha. 2009. Oxidative stress and mitochondrial dysfunction in sepsis: a potential therapy with mitochondria-targeted antioxidants. Infectious Disorders Drug Targets 9: 376–389.CrossRefPubMed

54.

Prauchner, Carlos André. 2017. Oxidative stress in sepsis: pathophysiological implications justifying antioxidant co-therapy. Burns 43: 471–485. https://doi.org/10.1016/j.burns.2016.09.023.CrossRefPubMed

55.

Esteban-Zubero, Eduardo, M.A. Alatorre-Jimenez, L. Lopez-Pingarron, M.C. Reyes-Gonzales, P. Almeida-Souza, A. Cantin-Golet, F.J. Ruiz-Ruiz, D.-X. Tan, J.J. Garcia, and R.J. Reiter. 2016. Melatonin’s role in preventing toxin-related and sepsis-mediated hepatic damage: a review. Pharmacological Research 105: 108–120. https://doi.org/10.1016/j.phrs.2016.01.018.CrossRefPubMed

56.

Makled, Mirhan N., M.S. El-Awady, R.R. Abdelaziz, N. Atwan, E.T. Guns, N.M. Gameil, A.B. Shehab El-Din, and E.M. Ammar. 2016. Pomegranate protects liver against cecal ligation and puncture-induced oxidative stress and inflammation in rats through TLR4/NF-kappaB pathway inhibition. Environmental Toxicology and Pharmacology 43: 182–192. https://doi.org/10.1016/j.etap.2016.03.011.CrossRefPubMed

57.

Xiao, Xuefei, M. Yang, D. Sun, and S. Sun. 2012. Curcumin protects against sepsis-induced acute lung injury in rats. Journal of Surgical Research 176: e31–e39. https://doi.org/10.1016/j.jss.2011.11.1032.CrossRefPubMed

58.

Liu, Chun-Hong, W.-D. Zhang, J.-J. Wang, and S.-D. Feng. 2016. Senegenin ameliorate acute lung injury through reduction of oxidative stress and inhibition of inflammation in cecal ligation and puncture-induced sepsis rats. Inflammation 39: 900–906. https://doi.org/10.1007/s10753-016-0322-6.CrossRefPubMed

59.

Aydin, Sevtap, T.T. Sahin, M. Bacanli, G. Taner, A.A. Basaran, M. Aydin, and N. Basaran. 2016. Resveratrol protects sepsis-induced oxidative DNA damage in liver and kidney of rats. Balkan Medical Journal 33: 594–601. https://doi.org/10.5152/balkanmedj.2016.15516.CrossRefPubMedPubMedCentral

60.

Taner, Gokce, S. Aydin, M. Bacanli, Z. Sarigol, T. Sahin, A.A. Basaran, and N. Basaran. 2014. Modulating effects of pycnogenol(R) on oxidative stress and DNA damage induced by sepsis in rats. Phytotherapy Research: PTR 28: 1692–1700. https://doi.org/10.1002/ptr.5184.CrossRefPubMed

61.

Mittal, Manish, M.R. Siddiqui, K. Tran, S.P. Reddy, and A.B. Malik. 2014. Reactive oxygen species in inflammation and tissue injury. Antioxidants & Redox Signaling 20: 1126–1167. https://doi.org/10.1089/ars.2012.5149.CrossRef

62.

Sies, Helmut. 2014. Role of metabolic H₂O₂ generation: redox signaling and oxidative stress. The Journal of Biological Chemistry 289: 8735–8741. https://doi.org/10.1074/jbc.R113.544635.CrossRefPubMedPubMedCentral

63.

Nguyen, Truyen, P. Nioi, and C.B. Pickett. 2009. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. The Journal of Biological Chemistry 284: 13291–13295. https://doi.org/10.1074/jbc.R900010200.CrossRefPubMedPubMedCentral

64.

Brennan, Melanie S., M.F. Matos, K.E. Richter, B. Li, and R.H. Scannevin. 2017. The NRF2 transcriptional target, OSGIN1, contributes to monomethyl fumarate-mediated cytoprotection in human astrocytes. Scientific Reports 7: 42054. https://doi.org/10.1038/srep42054.CrossRefPubMedPubMedCentral

65.

Miao, Weimin, L Hu, P J Scrivens, and G Batist. 2005. Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway: direct cross-talk between phase I and II drug-metabolizing enzymes. The Journal of Biological Chemistry 280. United States: 20340–20348. https://doi.org/10.1074/jbc.M412081200.

66.

Zhao, Xiurong, G. Sun, J. Zhang, S.-M. Ting, N. Gonzales, and J. Aronowski. 2015. Dimethyl fumarate protects brain from damage produced by intracerebral hemorrhage by mechanism involving Nrf2. Stroke 46: 1923–1928. https://doi.org/10.1161/STROKEAHA.115.009398.CrossRefPubMedPubMedCentral

67.

Ishii, T., K. Itoh, S. Takahashi, H. Sato, T. Yanagawa, Y. Katoh, S. Bannai, and M. Yamamoto. 2000. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. The Journal of Biological Chemistry 275: 16023–16029.CrossRefPubMed

68.

Shen, Guoxiang, C. Xu, R. Hu, M.R. Jain, A. Gopalkrishnan, S. Nair, M.-T. Huang, J.Y. Chan, and A.-N.T. Kong. 2006. Modulation of nuclear factor E2-related factor 2-mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin. Molecular Cancer Therapeutics 5: 39–51. https://doi.org/10.1158/1535-7163.MCT-05-0293.CrossRefPubMed

69.

Pan, Hao, H. Wang, X. Wang, L. Zhu, and L. Mao. 2012. The absence of Nrf2 enhances NF-kappaB-dependent inflammation following scratch injury in mouse primary cultured astrocytes. Mediators of Inflammation 2012: 217580. https://doi.org/10.1155/2012/217580.CrossRefPubMedPubMedCentral

70.

Iizuka, Takashi, Y. Ishii, K. Itoh, T. Kiwamoto, T. Kimura, Y. Matsuno, Y. Morishima, et al. 2005. Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema. Genes to Cells: Devoted to Molecular & Cellular Mechanisms 10: 1113–1125. https://doi.org/10.1111/j.1365-2443.2005.00905.x.CrossRef

71.

Jin, Wei, H. Wang, Y. Ji, Q. Hu, W. Yan, G. Chen, and H. Yin. 2008. Increased intestinal inflammatory response and gut barrier dysfunction in Nrf2-deficient mice after traumatic brain injury. Cytokine 44: 135–140. https://doi.org/10.1016/j.cyto.2008.07.005.CrossRefPubMed

72.

Jin, Wei, L. Zhu, Q. Guan, G. Chen, Q.F. Wang, H. Xia Yin, C.H. Hang, J.X. Shi, and H.D. Wang. 2008. Influence of Nrf2 genotype on pulmonary NF-kappaB activity and inflammatory response after traumatic brain injury. Annals of Clinical and Laboratory Science 38: 221–227.PubMed

73.

Selvaraj, Vellaisamy, N. Nepal, S. Rogers, N.D.P.K. Manne, R. Arvapalli, K.M. Rice, S. Asano, et al. 2015. Inhibition of MAP kinase/NF-kB mediated signaling and attenuation of lipopolysaccharide induced severe sepsis by cerium oxide nanoparticles. Biomaterials 59: 160–171. https://doi.org/10.1016/j.biomaterials.2015.04.025.CrossRefPubMedPubMedCentral

74.

Lolis, Elias, and Richard Bucala. 2003. Therapeutic approaches to innate immunity: Severe sepsis and septic shock. Nature Reviews. Drug Discovery 2: 635–645. https://doi.org/10.1038/nrd1153.CrossRefPubMed

75.

Spasojevic, Ivan, B. Obradovic, and S. Spasic. 2012. Bench-to-bedside review: neonatal sepsis-redox processes in pathogenesis. Critical Care 16: 221. https://doi.org/10.1186/cc11183.CrossRefPubMedPubMedCentral

76.

Loewe, Robert, W. Holnthoner, M. Groger, M. Pillinger, F. Gruber, D. Mechtcheriakova, E. Hofer, K. Wolff, and P. Petzelbauer. 2002. Dimethylfumarate inhibits TNF-induced nuclear entry of NF-kappa B/p65 in human endothelial cells. Journal of Immunology 168: 4781–4787.CrossRef

77.

Seidel, P., I. Merfort, J.M. Hughes, B.G.G. Oliver, M. Tamm, and M. Roth. 2009. Dimethylfumarate inhibits NF-{kappa}B function at multiple levels to limit airway smooth muscle cell cytokine secretion. American Journal of Physiology. Lung Cellular and Molecular Physiology 297: L326–L339. https://doi.org/10.1152/ajplung.90624.2008.CrossRefPubMed

78.

Schilling, S., S. Goelz, R. Linker, F. Luehder, and R. Gold. 2006. Fumaric acid esters are effective in chronic experimental autoimmune encephalomyelitis and suppress macrophage infiltration. Clinical and Experimental Immunology 145: 101–107. https://doi.org/10.1111/j.1365-2249.2006.03094.x.CrossRefPubMedPubMedCentral

79.

Casili, Giovanna, M. Cordaro, D. Impellizzeri, G. Bruschetta, I. Paterniti, S. Cuzzocrea, and E. Esposito. 2016. Dimethyl fumarate reduces inflammatory responses in experimental colitis. Journal of Crohn’s and Colitis 10: 472–483. https://doi.org/10.1093/ecco-jcc/jjv231.CrossRefPubMed

80.

Han, Ranran, J Xiao, H Zhai, and J Hao. 2016. Dimethyl fumarate attenuates experimental autoimmune neuritis through the nuclear factor erythroid-derived 2-related factor 2/hemoxygenase-1 pathway by altering the balance of M1/M2 macrophages. Journal of Neuroinflammation 13. Journal of Neuroinflammation: 97. https://doi.org/10.1186/s12974-016-0559-x.

81.

Robles, Lourdes, N.D. Vaziri, S. Li, C. Takasu, Y. Masuda, K. Vo, S.H. Farzaneh, M.J. Stamos, and H. Ichii. 2015. Dimethyl fumarate ameliorates acute pancreatitis in rodent. Pancreas 44: 441–447. https://doi.org/10.1097/MPA.0000000000000275.PubMedPubMedCentral

82.

Meili-Butz, Silvia, T. Niermann, E. Fasler-Kan, V. Barbosa, N. Butz, D. John, M. Brink, P.T. Buser, and C.E. Zaugg. 2008. Dimethyl fumarate, a small molecule drug for psoriasis, inhibits nuclear factor-kappaB and reduces myocardial infarct size in rats. European Journal of Pharmacology 586: 251–258. https://doi.org/10.1016/j.ejphar.2008.02.038.CrossRefPubMed

Title: Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats
Authors: 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
Publication date: 01-02-2018
Publisher: Springer US
Published in: Inflammation / Issue 1/2018
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-017-0689-z

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

Illustration of figure on mountain summit/© Orapun / Stock.adobe.com, STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2018

The Regulatory Roles of Toll-Like Receptor 4 in Secretions of Type 1/Type 2 Relative Cytokines by Splenocytes and Dendritic Cells Exposed to Clonorchis sinensis Excretory/Secretory Products

Establishment of S100A8 Transgenic Rats to Understand Innate Property of S100A8 and Its Immunological Role

The Pyrazole Derivative BTP2 Attenuates IgG Immune Complex-induced Inflammation

A Novel Role of a Chemotherapeutic Agent in a Rat Model of Endotoxemia: Modulation of the STAT-3 Signaling Pathway

NLRP3 Inflammasome Activation in a Transgenic Amyotrophic Lateral Sclerosis Model

Protective Effects of Chymostatin on Paraquat-Induced Acute Lung Injury in Mice

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage