scholarly journals Proposed Neuroimmune Roles of Dimethyl Fumarate, Bupropion, S-Adenosylmethionine, and Vitamin D3 in Affording a Chronically Ill Patient Sustained Relief from Inflammation and Major Depression

2020 ◽  
Vol 10 (9) ◽  
pp. 600 ◽  
Author(s):  
Navzer D. Sachinvala ◽  
Naozumi Teramoto ◽  
Angeline Stergiou
Keyword(s):  
Oxidative Stress ◽  
Major Depression ◽  
Vitamin D3 ◽  
Sphenoid Sinus ◽  
Vision Loss ◽  
Chronically Ill ◽  
Dimethyl Fumarate ◽  
Peripheral Tissues ◽  
Physical Exercises ◽  
Literature Searches

We had discussed earlier that, after most of the primary author’s multiple sclerosis (MS) symptoms were lessened by prior neuroimmune therapies, use of dimethyl fumarate (DMF) gradually subdued his asthma and urticaria symptoms, as well as his MS-related intercostal cramping; and bupropion supplemented with S-adenosylmethionine (SAMe) and vitamin D3 (vit-D3) helped remit major depression (MD). Furthermore, the same cocktail (bupropion plus supplements), along with previously discussed routines (yoga, meditation, physical exercises, and timely use of medications for other illnesses), continued to subdue MD during new difficulties with craniopharyngioma, which caused bitemporal vision loss; sphenoid sinus infections, which caused cranial nerve-VI (CN6) palsy and diplopia; and through their treatments. Impressed with the benefit the four compounds provided, in this manuscript, we focus on explaining current neuroimmune literature proposals on how: (1) DMF impedes inflammation, oxidative stress, and cell death in CNS and peripheral tissues; (2) Bupropion curbs anxiety, MD, and enhances alertness, libido, and moods; (3) SAMe silences oxidative stress and depression by multiple mechanisms; and (4) Vit-D3 helps brain development and functioning and subdues inflammation. We realize that herein we have reviewed proposed mechanisms of remedies we discovered by literature searches and physician assisted auto-experimentation; and our methods might not work with other patients. We present our experiences so readers are heartened to reflect upon their own observations in peer-reviewed forums and make available a wide body of information for the chronically ill and their physicians to benefit from.

Effect of vitamin D treatment on VDR expression in primary cerebral cortical cells in induced oxidative stress

2020 ◽  
pp. 1-10
Author(s):  
Ebtesam Alsulami ◽  
Majed Alokail ◽  
Amani Alghamedi ◽  
Abir Alamro ◽  
Samina Haq
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Vitamin D3 ◽  
Cultured Cells ◽  
Neuroprotective Effect ◽  
Sandwich Elisa ◽  
Stress Protein ◽  
Neuronal Cultures ◽  
Primary Neuronal Cultures ◽  
Peripheral Tissues

BACKGROUND: In addition to calcium and phosphate homeostasis in peripheral tissues; vitamin D performs a neuroprotection role in the nervous system. The neuroprotective actions of vitamin D include: increasing vitamin D receptor (VDR) expression, control glutathione synthesis and nitric oxide synthase activity and induce neurotrophins such as nerve growth factor (NGF). VDR mediates cellular actions, and biological responses of the vitamin D. OBJECTIVE: To study the effect of VDR and NGF expression levels by vitamin D3 treatment in induced oxidative stress in primary cortical neuronal cultures. METHOD: Primary neuronal cultures were set up from the cortex region of neonatal rat’s brain. They were cultured for up to 72 h in the presence of 0.25μg/ml vitamin D3. These cells were exposed to 0.5 mM H2O2 for two hours before collecting cell pellet and medium for biochemical assays. Control and H2O2 treated cells were cultured in the absence of vitamin D3 treatment. Sandwich ELISA was used to study NGF expression. Western blotting and Immunofluorescence of cultured cells were used to estimate the expression of VDR. RESULTS: Vitamin D3 treatment increased more significantly (P <  0.001) NGF levels with and without induced oxidative stress. Protein expression studies confirmed the positive correlation between VDR expression and vitamin D3 treatment after 72 h in culture. Moreover, pre-treating the cells with vitamin D3 before H2O2 exposure significantly increase (P <  0.05) VDR expression in comparison with the cells exposed to H2O2 alone. CONCLUSION: The neuroprotective effect of vitamin D3 against oxidative stress could be through up-regulating VDR and NGF levels.

Melatonin: a novel strategy for prevention of obesity and fat accumulation in peripheral organs through the improvements of circadian rhythms and antioxidative capacity

2020 ◽  
Vol 3 (1) ◽  
pp. 58-76 ◽  
Author(s):  
Bohan Rong ◽  
Qiong Wu ◽  
Chao Sun
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Regulatory Mechanisms ◽  
Antioxidative Capacity ◽  
Unicellular Alga ◽  
Peripheral Tissues ◽  
Peripheral Organs ◽  
Regulatory Effects ◽  
Novel Strategy

Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and its contribution to protection against oxidative stress in organisms including unicellular alga, animals and plants. Currently, the bio-regulatory effects of melatonin on the physiology of various peripheral tissues have drawn a great attention of scientists. Although melatonin was previously defined as a neurohormone secreted from pineal gland, recently it has been identified that virtually, every cell has the capacity to synthesize melatonin and the locally generated melatonin has multiple pathophysiological functions, including regulations of obesity and metabolic syndromes. Herein, we focus on the effects of melatonin on fat deposition in various peripheral organs/tissues. The two important regulatory mechanisms related to the topic, i.e., the improvements of circadian rhythms and antioxidative capacity will be thoroughly discussed since they are linked to several biomarkers involved in obesity and energy imbalance, including metabolism and immunity. Furthermore, several other functions of melatonin which may serve to prevent or promote obesity and energy dysmetabolism-induced pathological states are also addressed. The organs of special interest include liver, pancreas, skeletal muscle, adipose tissue and the gut microbiota.

Protective effect of GSK-3β/Nrf2 mediated by dimethyl fumarate in middle cerebral artery embolization reperfusion rat model

2021 ◽  
Vol 18 ◽  
Author(s):  
Yuan Li ◽  
Lan Chu ◽  
Chunfeng Liu ◽  
Zongyi Zha ◽  
Yuanlu Shu
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Sham Group ◽  
Infarct Volume ◽  
Dimethyl Fumarate ◽  
Control Group ◽  
Related Factor ◽  
Nissl Staining ◽  
Gsk 3Β ◽  
Nrf2 Expression

Aim: This study investigated the protective effect of dimethyl fumarate (DMF) in rats by mediating GSK3-β/Nrf2 using the middle cerebral artery embolization reperfusion (MCAO/R) rat model. Background: After an acute ischemic stroke (AIS), oxidative stress occurs. Dimethyl fumarate (DMF), a nuclear factor-E2-related factor 2 (Nrf2) activator, approved by the US Food and Drug Administration (FDA), was observed to regulate the Nrf2 pathway by acting as an anti-oxidative stress agent; however, whether this agent is involved in inhibiting GSK-3β remains to be established. Methods: DMF model was used to explore the effects of GSK-3β on Nrf2 expression level, Nrf2-ARE binding activity and Nrf2/ARE downstream expression level of anti-oxidant stress protein in Cerebral ischemia-reperfusion injury (CIRI). 60 rats were randomly divided into Sham group, MCAO/R group, solvent control group (DMSO group) and DMF treatment group, with 15 rats in each group. The MCAO/R, DMSO and DMF groups were considered in the MCAO/R model using the modified thread embolization method. In contrast, the Sham group was only anaesthetized and disinfected, and tissue muscle was dissected without inserting suture emboli. DMF group was gavaged with 45mg/kg per day of DMF, DMSO control group was gavaged with DMSO of equal volume, while MCAO/R group was only modeled without any intragastric treatment. The rats were treated seven days after the operation, and a neurological function Longa score was estimated. The rats were sacrificed seven days later, and the infarct volume was assessed by TTC staining. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in rat brain tissue. Nissl staining was used to observe the expression of neurons in the infarcted cortex. Western blotting (WB) was used to observe the protein expression levels of glycogen synthase kinase 3β(GSK-3β), nuclear factor E2-related factor 2 (Nrf2), downstream heme oxygenase 1 (HO1) and NADPH quinone oxidoreductase 1 (NQO1) in four groups. The expression levels of GSK-3β and Nrf2 in the four groups were observed by immunohistochemistry and immunofluorescence. Results: (1) The Longa score of the MCAO/R, DMSO and DMF groups was found to be higher compared to the Sham group, indicating successful operation. The Longa score of the DMF group was lower than that of the other three groups 4-7 days after surgery (P<0.05). (2) HE and Nissl staining showed that the DMF group had lower neuron necrosis and higher gliosis compared to the control groups. (3) TTC staining results showed that the infarct volume of the DMF group was significantly smaller than the MCAO/R and DMSO groups. (4) Protein results showed that the GSK-3β expression in the DMF group was lower than that in all groups, while the expression of Nrf2, HO1 and NQO1 was higher compared to other groups. Conclusion: DMF can reduce neurological deficits and infarct size in the MCAO/R model. The protective effect may be related to decreased GSK-3β expression and increased Nrf2 expression, which may play a role in anti-oxidative stress.

scholarly journals Effects of a Single Oral Megadose of Vitamin D3 on Inflammation and Oxidative Stress Markers in Overweight and Obese Women: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

2021 ◽  
Vol Volume 14 ◽  
pp. 525-534
Author(s):  
Laine de Carvalho Guerra Pessoa Mamede ◽  
Rafaela Lira Formiga Cavalcanti de Lima ◽  
Alexandre Sérgio Silva ◽  
João Carlos Lima Rodrigues Pita ◽  
Nadjeanny Ingrid Galdino Gomes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trial ◽  
Vitamin D3 ◽  
Controlled Clinical Trial ◽  
Oxidative Stress Markers ◽  
Obese Women ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Stress Markers ◽  
And Oxidative Stress

scholarly journals Superoxide Dismutase-1 Induced Oxidative Stress Mediated Apoptosis in Murine Retinal Pigment Epithelial Cells

2019 ◽  
Vol 8 (4S2) ◽  
pp. 463-466
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Vision Loss ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Superoxide Dismutase 1 ◽  
Central Vision Loss ◽  
Age Related ◽  
Pigment Epithelial Cells

Age related macular degeneration (AMD) is a complicated ocular disease which occurs in elderly people and leads to central vision loss. The AMD generated because of overproduction of oxidative stress which leads to RPE cell death. The present study investigates whether SOD1 induced MRPE cell death based on that overexpression of SOD1 in MRPE cells which induced cell death. The SOD1 gradually increased ROS production and fragmentation of nuclei. To explore the ER stress persuaded UPR via GRP78, and CHOP, protein expression level analyses were carried out by western blotting. Together, our results represent that SOD1 could possibly produce the oxidant induced MRPE cell death.

scholarly journals Oxidative Stress in Optic Neuropathies

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1538
Author(s):  
Berta Sanz-Morello ◽  
Hamid Ahmadi ◽  
Rupali Vohra ◽  
Sarkis Saruhanian ◽  
Kristine Karla Freude ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Redox System ◽  
Ischemic Optic Neuropathy ◽  
Retinal Ganglion ◽  
Oxidative Stress Biomarkers ◽  
Optic Disc Drusen ◽  
Advanced Stages

Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber’s hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.

scholarly journals Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress

2021 ◽  
Vol 14 (8) ◽  
pp. 1260-1273
Author(s):  
Zi-Yan Cai ◽  
◽  
Ke Liu ◽  
Xuan-Chu Duan ◽  
◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vision Loss ◽  
Eye Diseases ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Classical Pathway ◽  
Age Related ◽  
Important Relationship

Age-related eye diseases, including cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are the leading causes of vision loss in the world. Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye. The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body. This pathway is also active in the development of age-related eye diseases. A variety of drugs have been shown to treat age-related eye diseases through the Keap1-Nrf2-ARE (Kelch-like ECH-Associating protein 1- nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway. This review describes the role of oxidative stress in the development of age-related eye diseases, the function and regulation of the Keap1-Nrf2-ARE pathway, and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.

scholarly journals PGC-1α Protects RPE Cells of the Aging Retina against Oxidative Stress-Induced Degeneration through the Regulation of Senescence and Mitochondrial Quality Control. The Significance for AMD Pathogenesis

2018 ◽  
Vol 19 (8) ◽  
pp. 2317 ◽  
Author(s):  
Kai Kaarniranta ◽  
Jakub Kajdanek ◽  
Jan Morawiec ◽  
Elzbieta Pawlowska ◽  
Janusz Blasiak
Keyword(s):  
Oxidative Stress ◽  
Cellular Senescence ◽  
Mitochondrial Biogenesis ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Sirtuin 1 ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related

PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional coactivator of many genes involved in energy management and mitochondrial biogenesis. PGC-1α expression is associated with cellular senescence, organismal aging, and many age-related diseases, including AMD (age-related macular degeneration), an important global issue concerning vision loss. We and others have developed a model of AMD pathogenesis, in which stress-induced senescence of retinal pigment epithelium (RPE) cells leads to AMD-related pathological changes. PGC-1α can decrease oxidative stress, a key factor of AMD pathogenesis related to senescence, through upregulation of antioxidant enzymes and DNA damage response. PGC-1α is an important regulator of VEGF (vascular endothelial growth factor), which is targeted in the therapy of wet AMD, the most devastating form of AMD. Dysfunction of mitochondria induces cellular senescence associated with AMD pathogenesis. PGC-1α can improve mitochondrial biogenesis and negatively regulate senescence, although this function of PGC-1α in AMD needs further studies. Post-translational modifications of PGC-1α by AMPK (AMP kinase) and SIRT1 (sirtuin 1) are crucial for its activation and important in AMD pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document