Dimethyl Fumarate Limits Neuroinflammation and Oxidative Stress and Improves Cognitive Impairment After Polymicrobial Sepsis

2018 ◽  
Vol 34 (3) ◽  
pp. 418-430 ◽  
Author(s):  
Graciela Freitas Zarbato ◽  
Mariana Pereira de Souza Goldim ◽  
Amanda Della Giustina ◽  
Lucinéia Gainski Danielski ◽  
Khiany Mathias ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Dimethyl Fumarate ◽  
Polymicrobial Sepsis ◽  
And Oxidative Stress

scholarly journals GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1175
Author(s):  
Johanna Helmstädter ◽  
Karin Keppeler ◽  
Franziska Aust ◽  
Leonie Küster ◽  
Katie Frenis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Function ◽  
Vascular Inflammation ◽  
Cecal Ligation ◽  
Isometric Tension ◽  
Polymicrobial Sepsis ◽  
Dot Blot ◽  
Markers Of Inflammation ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.

scholarly journals Rapamycin attenuated zinc-induced tau phosphorylation and oxidative stress in animal model: Involvement of dual mTOR/p70S6K and Nrf2/HO-1 pathways

2021 ◽  
Author(s):  
Chencen Lai ◽  
Qian Chen ◽  
Yuanting Ding ◽  
Songbai Su ◽  
Heng Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Morris Water Maze ◽  
Zinc Sulfate ◽  
Water Maze ◽  
Tau Phosphorylation ◽  
Alzheimers Disease ◽  
Tau Pathology ◽  
Biochemical Assays ◽  
And Oxidative Stress

Alzheimers disease is pathologically featured by abnormal accumulation of amyloid-beta plaque, neurofibrillary tangles, oxidative stress, neuroinflammation, and neurodegeneration. Metal dysregulation including excessive zinc released by presynaptic neurons plays an important role in tau pathology and oxidase activation. The activities of mammalian target of rapamycin (mTOR)/ ribosomal S6 protein kinase (p70S6K) are elevated in the brains of patients with Alzheimers disease. Zinc induces tau hyperphosphorylation via mTOR/P70S6K activation in vitro. However, the involvement of mTOR/P70S6K pathway in zinc-induced oxidative stress, tau degeneration, synaptic and cognitive impairment, has not been fully elucidated in vivo. Here we assessed in the effect of pathological concentration of zinc in SH-SY5Y cells by using biochemical assays and immunofluorescence staining. Rats (n = 18, male) were lateral ventricularly-injected with zinc and treated with rapamycin (intraperitoneal injection) for one week and assessed using Morris water maze. Evaluation of the oxidative stress, tau phorsphylation and synaptic impairment were performed using the hippocampus tissue of the rats by biochemical assays and immunofluorescence staining. Results from Morris water maze showed that the capacity of spatial memory is impaired in zinc-treated rats. Zinc sulfate significantly increased the levels of P-mTOR Ser2448, P-p70S6K Thr389, and P-tau Ser356, and decreased levels of Nrf2 and HO-1 in SH-SY5Y cells and in zinc-treated rats compared with control groups. Increased expressions of reactive oxygen species were observed in zinc sulfate-induced SH-SY5Y cells as well as in the hippocampus of zinc-injected rats. Rapamycin, an inhibitor of mTOR, rescued the zinc-induced increases in mTOR/p70S6K activations, tau phosphorylation and oxidative stress, as well as Nrf2/HO-1 inactivation, cognitive impairment and synaptic impairment reduced the expression of synapse-related proteins in zinc-injected rats. In conclusion, our findings imply that rapamycin prevents zinc-induced cognitive impairment and protects neurons from tau pathology, oxidative stress and synaptic impairment, by decreasing mTOR/p70S6K hyperactivity and increasing Nrf2/HO-1 activity.

Effect of black mulberry (Morus nigra) extract treatment on cognitive impairment and oxidative stress status ofd-galactose-induced aging mice

2015 ◽  
Vol 54 (6) ◽  
pp. 1052-1064 ◽  
Author(s):  
Nergiz Hacer Turgut ◽  
Derya Guliz Mert ◽  
Haki Kara ◽  
Hatice Reyhan Egilmez ◽  
Emre Arslanbas ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Morus Nigra ◽  
Oxidative Stress Status ◽  
And Oxidative Stress

Vitamin D3 attenuates lipopolysaccharide-induced cognitive impairment in rats by inhibiting inflammation and oxidative stress

Life Sciences ◽  
2020 ◽  
Vol 253 ◽  
pp. 117703 ◽  
Author(s):  
Amin Mokhtari-Zaer ◽  
Mahmoud Hosseini ◽  
Hossein Salmani ◽  
Zohreh Arab ◽  
Parvin Zareian
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Vitamin D3 ◽  
And Oxidative Stress

scholarly journals Dimethyl Fumarate and Its Esters: A Drug with Broad Clinical Utility?

2020 ◽  
Vol 13 (10) ◽  
pp. 306 ◽  
Author(s):  
Stephanie Kourakis ◽  
Cara A. Timpani ◽  
Judy B. de Haan ◽  
Nuri Gueven ◽  
Dirk Fischer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dimethyl Fumarate ◽  
Immune Mediated ◽  
Relapsing Remitting ◽  
Favourable Safety ◽  
Potential Benefits ◽  
Monomethyl Fumarate ◽  
Relapsing Remitting Multiple Sclerosis ◽  
And Oxidative Stress ◽  
Acid Esters

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

scholarly journals Age-related cognitive impairment is associated with long-term neuroinflammation and oxidative stress in a mouse model of episodic systemic inflammation

2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Joana Costa d’Avila ◽  
Luciana Domett Siqueira ◽  
Aurélien Mazeraud ◽  
Estefania Pereira Azevedo ◽  
Debora Foguel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Systemic Inflammation ◽  
Age Related ◽  
And Oxidative Stress
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