scholarly journals Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 416
Author(s):  
Yoelvis Garcia-Mesa ◽  
He N. Xu ◽  
Patricia Vance ◽  
Analise L. Gruenewald ◽  
Rolando Garza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Antioxidant Enzymes ◽  
Antioxidant Enzyme ◽  
Rhesus Macaques ◽  
Dimethyl Fumarate ◽  
Brain Regions ◽  
Synaptic Proteins ◽  
Persons Living With Hiv ◽  
The Brain

Dimethyl fumarate (DMF), an antioxidant/anti-inflammatory drug approved for the treatment of multiple sclerosis, induces antioxidant enzymes, in part through transcriptional upregulation. We hypothesized that DMF administration to simian immunodeficiency virus (SIV)-infected rhesus macaques would induce antioxidant enzyme expression and reduce oxidative injury and inflammation throughout the brain. Nine SIV-infected, CD8+-T-lymphocyte-depleted rhesus macaques were studied. Five received oral DMF prior to the SIV infection and through to the necropsy day. Protein expression was analyzed in 11 brain regions, as well as the thymus, liver, and spleen, using Western blot and immunohistochemistry for antioxidant, inflammatory, and neuronal proteins. Additionally, oxidative stress was determined in brain sections using immunohistochemistry (8-OHdG, 3NT) and optical redox imaging of oxidized flavoproteins containing flavin adenine dinucleotide (Fp) and reduced nicotinamide adenine dinucleotide (NADH). The DMF treatment was associated with no changes in virus replication; higher expressions of the antioxidant enzymes NQO1, GPX1, and HO-1 in the brain and PRDX1 and HO-2 in the spleen; lower levels of 8-OHdG and 3NT; a lower optical redox ratio. The DMF treatment was also associated with increased expressions of cell-adhesion molecules (VCAM-1, ICAM-1) and no changes in HLA-DR, CD68, GFAP, NFL, or synaptic proteins. The concordantly increased brain antioxidant enzyme expressions and reduced oxidative stress in DMF-treated SIV-infected macaques suggest that DMF could limit oxidative stress throughout the brain through effective induction of the endogenous antioxidant response. We propose that DMF could potentially induce neuroprotective brain responses in persons living with HIV.

The effects of crocin (active contstituent of saffron) treatment on brain antioxidant enzyme mRNA levels in diabetic rats / Diyabetik ratlarda safranın aktif içeriği olan krosin tedavisinin beyindeki antioksidan enzimlerin mRNA seviyeleri üzerine etkisi

2016 ◽  
Vol 41 (2) ◽  
Author(s):  
Eyüp Altınöz ◽  
Cemal Ekici ◽  
Berna Özyazgan ◽  
Yılmaz Çiğremiş
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Mrna Expression ◽  
Antioxidant Enzyme ◽  
Diabetic Rats ◽  
Control Group ◽  
Mrna Levels ◽  
The Brain ◽  
And Oxidative Stress

AbstractObjective: The aim of the present study is to evaluate the effect of crocin on mRNA expression of antioxidant enzymes, SOD, CAT and GPX in the brain of the STZ induced diabetic rats.Methods: Thirty animals randomized in three groups containing ten animals in each group as follows; control (non-diabetic rats), DM (STZ-induced untreated diabetic rats), DM+crocin (STZ-induced diabetic rats treated with crocin,). Crocin was given at a dose of 20 mg/kg bw/day by gavage for 21 days.Results: STZ injection caused a significant increase in mRNA expression of antioxidant enzymes, SOD, CAT and GPX when compared to control group. Crocin given to diabetic rats significantly decreased mRNA expression of antioxidant enzymes, SOD, CAT and GPX when compared to DM group.Conclusion: The present study demonstrates that crocin can modulate mRNA expression of antioxidant enzymes, SOD, CAT and GPX and oxidative stress in the brain of the STZ induced diabetic rats.

scholarly journals 3,3′-Diindolylmethane Promotes BDNF and Antioxidant Enzyme Formation via TrkB/Akt Pathway Activation for Neuroprotection against Oxidative Stress-Induced Apoptosis in Hippocampal Neuronal Cells

Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 3 ◽  
Author(s):  
Bo Dam Lee ◽  
Jae-Myung Yoo ◽  
Seong Yeon Baek ◽  
Fu Yi Li ◽  
Dai-Eun Sok ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Neurodegenerative Diseases ◽  
Antioxidant Enzyme ◽  
Neuronal Cells ◽  
Akt Pathway ◽  
Heme Oxygenase 1 ◽  
Enzyme Formation ◽  
Induced Apoptosis

3,3′-Diindolylmethane (DIM), a metabolite of indole-3-carbinol present in Brassicaceae vegetables, possesses various health-promoting effects. Nonetheless, the effect of DIM on neurodegenerative diseases has not been elucidated clearly. In this study, we hypothesized DIM may protect neuronal cells against oxidative stress-induced apoptosis by promoting the formation of brain-derived neurotrophic factor (BDNF) and antioxidant enzymes through stabilizing the activation of the tropomyosin-related kinase receptor B (TrkB) cascade and we investigated the effect of DIM on oxidative stress-mediated neurodegenerative models. DIM protected neuronal cells against oxidative stress-induced apoptosis by regulating the expression of apoptosis-related proteins in glutamate-treated HT-22 cells. Additionally, DIM improved the expression of BDNF and antioxidant enzymes, such as heme oxygenase-1, glutamate-cysteine ligase catalytic subunit, and NAD(P)H quinine oxidoreductase-1, by promoting the activation of the TrkB/protein kinase B (Akt) pathway in the cells. Consistent with in vitro studies, DIM attenuated memory impairment by protecting hippocampal neuronal cells against oxidative damage in scopolamine-treated mice. Conclusionally, DIM exerted neuroprotective and antioxidant actions through the activation of both BDNF production and antioxidant enzyme formation in accordance with the TrkB/Akt pathway in neuronal cells. Such an effect of DIM may provide information for the application of DIM in the prevention of and therapy for neurodegenerative diseases.

scholarly journals Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1018
Author(s):  
Caitlyn A. Mullins ◽  
Ritchel B. Gannaban ◽  
Md Shahjalal Khan ◽  
Harsh Shah ◽  
Md Abu B. Siddik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Homeostasis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Obesity Prevalence ◽  
Beneficial Effects ◽  
The Brain

Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.

scholarly journals Immunology and Oxidative Stress in Multiple Sclerosis: Clinical and Basic Approach

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Genaro G. Ortiz ◽  
Fermín P. Pacheco-Moisés ◽  
Oscar K. Bitzer-Quintero ◽  
Ana C. Ramírez-Anguiano ◽  
Luis J. Flores-Alvarado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Tissue Injury ◽  
Autoimmune Disorder ◽  
Demyelinating Lesions ◽  
The Central Nervous System ◽  
The Brain ◽  
And Oxidative Stress

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

Queuine promotes antioxidant defence system by activating cellular antioxidant enzyme activities in cancer

2008 ◽  
Vol 28 (2) ◽  
pp. 73-81 ◽  
Author(s):  
Chandramani Pathak ◽  
Yogesh K. Jaiswal ◽  
Manjula Vinayak
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Antioxidant Enzyme ◽  
Enzyme Activities ◽  
Mouse Liver ◽  
Similar Rate ◽  
Antioxidant Enzyme Activities ◽  
Antioxidant Defence ◽  
Defence System ◽  
Antioxidant Defence System

Constant generation of ROS (reactive oxygen species) during normal cellular metabolism of an organism is generally balanced by a similar rate of consumption by antioxidants. Imbalance between ROS production and antioxidant defence results in an increased level of ROS, causing oxidative stress, which leads to promotion of malignancy. Queuine is a hyper-modified base analogue of guanine, found at the first anticodon position of the Q-family of tRNAs. These tRNAs are completely modified with respect to queuosine in terminally differentiated somatic cells; however, hypo-modification of Q-tRNAs is closely associated with cell proliferation. Q-tRNA modification is essential for normal development, differentiation and cellular function. Queuine is a nutrient factor for eukaryotes. It is found to promote the cellular antioxidant defence system and inhibit tumorigenesis. The activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase are found to be low in the DLAT (Dalton's lymphoma ascites transplanted) mouse liver compared with normal mouse liver. However, exogenous administration of queuine to the DLAT cancerous mouse improves the activities of antioxidant enzymes. These results suggest that queuine promotes the antioxidant defence system by increasing antioxidant enzyme activities and in turn inhibits oxidative stress and tumorigenesis.

Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress

2016 ◽  
Vol 94 (10) ◽  
pp. 1074-1082 ◽  
Author(s):  
Dragan Hrncic ◽  
Jelena Mikić ◽  
Aleksandra Rasic-Markovic ◽  
Milica Velimirović ◽  
Tihomir Stojković ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Open Field ◽  
Wistar Rats ◽  
Brain Regions ◽  
Oxidative Status ◽  
Standard Diet ◽  
Male Wistar Rats ◽  
Brain Oxidative Stress ◽  
The Brain

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light–dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

scholarly journals Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Alfonso Díaz ◽  
Samuel Treviño ◽  
Jorge Guevara ◽  
Guadalupe Muñoz-Arenas ◽  
Eduardo Brambila ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Inflammatory Response ◽  
Temporal Cortex ◽  
Energy Drink ◽  
Brain Regions ◽  
Adult Rats ◽  
Mechanisms Of Toxicity ◽  
The Brain ◽  
And Oxidative Stress

Energy drinks (EDs) are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis) at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx) and hippocampus (Hp) of adult rats (90 days old). Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats.

Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure

2008 ◽  
Vol 24 (4) ◽  
pp. 247-256 ◽  
Author(s):  
D Mishra ◽  
SJS Flora
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Drinking Water ◽  
Wistar Rats ◽  
Arsenic Exposure ◽  
Brain Regions ◽  
Single Strand ◽  
Male Wistar Rats ◽  
Chronic Arsenic Exposure ◽  
The Brain

Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain – parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50 ppm sodium arsenite in drinking water) for 10 months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

scholarly journals Isomeric O-methyl cannabidiolquinones with dual BACH1/NRF2 activity

2020 ◽  
Author(s):  
Laura Casares ◽  
Juan Diego Unciti ◽  
Maria Eugenia Prados ◽  
Diego Caprioglio ◽  
Maureen Higgins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Neurodegenerative Diseases ◽  
Cell Models ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
The Brain

ABSTRACTOxidative stress and inflammation in the brain are two key hallmarks of neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, Huntington’s and multiple sclerosis. The axis NRF2-BACH1 has anti-inflammatory and anti-oxidant properties that could be exploited pharmacologically to obtain neuroprotective effects. Activation of NRF2 or inhibition of BACH1 are, individually, promising therapeutic approaches for NDs. Compounds with dual activity as NRF2 activators and BACH1 inhibitors, could therefore potentially provide a more robust antioxidant and anti-inflammatory effects, with an overall better neuroprotective outcome. The phytocannabinoid cannabidiol (CBD) inhibits BACH1 but lacks significant NRF2 activating properties. Based on this scaffold, we have developed a novel CBD derivative that is highly effective at both inhibiting BACH1 and activating NRF2. This new CBD derivative provides neuroprotection in cell models of relevance to Huntington’s disease, setting the basis for further developments in vivo.

Sign in / Sign up

Export Citation Format

Share Document