Protective Effect of Dimethyl Fumarate on an Oxidative Stress Model Induced by Sodium Nitroprusside in Mice

Kume, Toshiaki; Suenaga, Aya; Izumi, Yasukatsu; Akaike, Akinori

doi:10.1248/bpb.b16-00134

Cited by 9 publications

(7 citation statements)

References 16 publications

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“…It may be responsible for neuroprotection [53]. Another effect of DMF may be associated with the activation of heme oxygenase-1 [146]. The use of a signaling pathway of the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2-antioxidant-responsive element (Keap1-Nrf2-ARE) in vivo and in vitro leads to the downregulation of OS and inflammation, activated by DMF which may protect the nervous tissue against subarachnoid hemorrhage induced brain injury in rats [147].…”

Section: The Relationship Between Immunomodulatory Therapy Os Anmentioning

confidence: 99%

New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

Adamczyk

Adamczyk-Sowa

2016

Oxidative Medicine and Cellular Longevity

115

100

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Multiple sclerosis (MS) is a multifactorial disease of the central nervous system (CNS) characterized by an inflammatory process and demyelination. The etiology of the disease is still not fully understood. Therefore, finding new etiological factors is of such crucial importance. It is suspected that the development of MS may be affected by oxidative stress (OS). In the acute phase OS initiates inflammatory processes and in the chronic phase it sustains neurodegeneration. Redox processes in MS are associated with mitochondrial dysfunction, dysregulation of axonal bioenergetics, iron accumulation in the brain, impaired oxidant/antioxidant balance, and OS memory. The present paper is a review of the current literature about the role of OS in MS and it focuses on all major aspects. The article explains the mechanisms of OS, reports unique biomarkers with regard to their clinical significance, and presents a poorly understood relationship between OS and neurodegeneration. It also provides novel methods of treatment, including the use of antioxidants and the role of antioxidants in neuroprotection. Furthermore, adding new drugs in the treatment of relapse may be useful. The article considers the significance of OS in the current treatment of MS patients.

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Section: The Relationship Between Immunomodulatory Therapy Os Anmentioning

confidence: 99%

New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

Adamczyk

Adamczyk-Sowa

2016

Oxidative Medicine and Cellular Longevity

115

100

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“…As a first-line treatment for multiple sclerosis, DMF can inhibit lipid peroxidation, and regulate free radical metabolism [28]. The findings from the present study showed that in STZ-induced hyperglycemic mice with experimental aortic atherosclerosis, DMF increased the expression of Nrf2, reduced aortic oxidation, and improved thoracic aortic endothelial function.…”

Section: Discussionmentioning

confidence: 53%

The Effects of Dimethyl Fumarate on Atherosclerosis in the Apolipoprotein E-Deficient Mouse Model with Streptozotocin-Induced Hyperglycemia Mediated By the Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element (Nrf2/ARE) Signaling Pathway

et al. 2019

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BackgroundThis study aimed to investigate the effects of dimethyl fumarate (DMF) on thoracic aortic atherosclerosis in the apolipoprotein E (apo-E)-deficient mouse model with streptozotocin (STZ)-induced hyperglycemia, and the signaling pathways involved.Material/MethodsEight-week-old ApoE−/− male mice (n=30) were randomly divided into three groups: the Control group (ApoE−/−) (n=10); the diabetic model (STZ) group (n=10); and the DMF-treated (25 mg/kg) diabetic model (DMF+STZ) group (n=10). The area of the thoracic aortic atherosclerosis was determined by histology. Reactive oxygen species (ROS) levels in mouse serum and homogenates of the thoracic aorta were determined by colorimetry. Levels of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase subunit gp91phox were detected by immunological hybridization, and levels of heme oxygenase-1 (HO-1) were measured by enzyme-linked immunosorbent assay (ELISA).ResultsCompared with the Control group, in the STZ group, the area of aortic atherosclerosis was significantly increased, the levels of serum and aortic ROS, HO-1, nuclear factor-κB (NF-κB), intercellular adhesion molecule 1 (ICAM-1), and gp91phox were increased, and nuclear factor erythroid 2-related factor 2 (Nrf2), endothelial nitric oxide synthase (eNOS), and phosphorylated eNOS (p-eNOS) were significantly reduced. Compared with the STZ group, in the DMF+STZ group, the area of aortic atherosclerosis was significantly reduced, the levels of serum and aortic ROS, HO-1, NF-κB, ICAM-1, and gp91phox were significantly reduced, and Nrf2, eNOS, and p-eNOS were significantly increased.ConclusionsIn the apo-E-deficient mouse model with STZ-induced hyperglycemia, DMF reduced the development of atherosclerosis of the thoracic aorta through the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway.

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“…Previous mechanistic studies suggested that the therapeutic mechanism of DMF is mainly involved in Nrf-2-dependent regulation of oxidative stress [ 19 , 20 ]. A series of evidence have shown that Nrf-2 is beneficial for autoimmune disorders and inflammatory diseases, such as multiple sclerosis and neurodegenerative diseases [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previous mechanistic studies suggested that the therapeutic mechanism of DMF is mainly involved in Nrf-2-dependent regulation of oxidative stress [19,20]. injected the mice at a dosage of 10 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress

Zhou

Xie

et al. 2021

Renal Failure

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Background Characterized by macrophage infiltration, renal inflammation during septic acute kidney injury (AKI) reveals a ubiquitous human health problem. Unfortunately, effective therapies with limited side effects are still lacking. This study is aiming to elucidate the role of Dimethyl fumarate (DMF) in macrophages against oxidative stress of septic AKI. Methods Balb/c mice were gavaged by 50 mg/kg DMF then injected with 10 mg/kg LPS by i.p. We examined LPS-induced renal dysfunction and histological features in murine kidneys. Raw264.7 macrophage cells were also treated with DMF and then induced by LPS. The mitotracker staining was used to follow mitochondria integrity by confocal microscopy. Flow cytometry measured the production of ROS by DCF-HDA and the expression of iNOS. Western blot detected the expression of Nrf-2 and Sirt1. Co-IP measured the interaction between Sirt1 and Nrf-2. Confocal microscopy observed the colocalization of Sirt1 and Nrf-2 in LPS-treated Raw264.7 macrophage cells. Results DMF ameliorated murine LPS nephritis with reduced blood urea nitrogen and serum creatinine, as well as decreased the histological alterations compared to the normal control. DMF significantly inhibited the expression of iNOS and reduced the production of nitrite in Raw264.7 cells following LPS treatment. Our study also revealed the role of DMF in protecting against intracellular ROS accumulation and mitochondria dysfunction in LPS-induced nephritis. DMF facilitated colocalization and interaction between Sirt1 and Nrf-2 in LPS-treated cells. Conclusions This study showed that DMF alleviated LPS-induced nephritis, indicating protective effects of DMF on macrophage against oxidative stress induced by LPS potentially involving Nrf-2-mediated pathway.

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Protective Effect of Dimethyl Fumarate on an Oxidative Stress Model Induced by Sodium Nitroprusside in Mice

Cited by 9 publications

References 16 publications

New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

New Insights into the Role of Oxidative Stress Mechanisms in the Pathophysiology and Treatment of Multiple Sclerosis

The Effects of Dimethyl Fumarate on Atherosclerosis in the Apolipoprotein E-Deficient Mouse Model with Streptozotocin-Induced Hyperglycemia Mediated By the Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element (Nrf2/ARE) Signaling Pathway

Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress

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