scholarly journals Repurposing Fumaric Acid Esters to Treat Conditions of Oxidative Stress and Inflammation: A Promising Emerging Approach with Broad Potential

2020 ◽  
Author(s):  
Ravirajsinh N. Jadeja ◽  
Folami L. Powell ◽  
Pamela M. Martin
Keyword(s):  
Oxidative Stress ◽  
Fumaric Acid ◽  
Potential Benefit ◽  
Dimethyl Fumarate ◽  
The United States ◽  
Clinical Implementation ◽  
Us Fda ◽  
Fumaria Officinalis ◽  
And Oxidative Stress ◽  
Acid Esters

The medicinal benefit of salts of fumaric acid and its esters (FAE), known as fumarates (mono and dimethyl fumarate), was realized many years ago. Early on, FAE were derived from plants and mushrooms (e.g., Fumaria officinalis, Boletus fomentarius var. pseudo-igniarius). The FAE containing formulation Fumaderm® was licensed in Germany for the treatment of psoriasis in 1994. Recently, a clinical formulation of dimethyl fumarate known as BG12 (Tecfidera) was approved for use in the United States, New Zealand, Australia, European Union, Switzerland, and Canada for the treatment of multiple sclerosis. Others and we have assessed the potential benefit of FAE in a number of disease conditions that are diverse with respect to etiology but unified with regard to the involvement of inflammation and oxidative stress. Hence, a FAE-based drug with robust anti-oxidative and anti-inflammatory effects that is already US-FDA approved is a perfect contender for repurposing and rapid clinical implementation for their management. There is a burgeoning literature on the use of FAE in the prevention and treatment of diseases, other than psoriasis and MS, in which oxidative stress and/or inflammation are prominent. This chapter highlights critical information gleaned from these studies, exposes lacunae of potential importance, and provides related perspectives.

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

2020 ◽  
Author(s):  
Stephanie Kourakis ◽  
Cara Timpani ◽  
Judy 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.

Nose-only water-pipe smoking effects on airway resistance, inflammation, and oxidative stress in mice

2013 ◽  
Vol 115 (9) ◽  
pp. 1316-1323 ◽  
Author(s):  
Abderrahim Nemmar ◽  
Haider Raza ◽  
Priya Yuvaraju ◽  
Sumaya Beegam ◽  
Annie John ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Airway Resistance ◽  
Reduced Glutathione ◽  
Mechanistic Explanation ◽  
The United States ◽  
Forced Oscillation Technique ◽  
Water Pipe ◽  
Respiratory Effects ◽  
And Oxidative Stress

Water-pipe smoking (WPS) is a common practice in the Middle East and is now gaining popularity in Europe and the United States. However, there is a limited number of studies on the respiratory effects of WPS. More specifically, the underlying pulmonary pathophysiological mechanisms related to WPS exposure are not understood. Presently, we assessed the respiratory effects of nose-only exposure to mainstream WPS generated by commercially available honey flavored “moasel ” tobacco. The duration of the session was 30 min/day and 5 days/wk for 1 mo. Control mice were exposed to air only. Here, we measured in BALB/c mice the airway resistance using forced-oscillation technique. Lung inflammation was assessed histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid, and oxidative stress was evaluated biochemically by measuring lipid peroxidation, reduced glutathione and several antioxidant enzymes. Pulmonary inflammation assessment showed an increase in neutrophil and lymphocyte numbers. Likewise, airway resistance was significantly increased in the WPS group compared with controls. Tumor necrosis factor α and interleukin 6 concentrations were significantly increased in BAL fluid. Lipid peroxidation in lung tissue was significantly increased whereas the level and activity of antioxidants including reduced glutathione, glutathione S transferase, and superoxide dismutase were all significantly decreased following WPS exposure, indicating the occurrence of oxidative stress. Moreover, carboxyhemoglobin levels were significantly increased in the WPS group. We conclude that 1-mo nose-only exposure to WPS significantly increased airway resistance, inflammation, and oxidative stress. Our results provide a mechanistic explanation for the limited clinical studies that reported the detrimental respiratory effects of WPS.

Abstract 371: DPPIV Inhibitor MK0626 Prevents Western Diet Induced Renal Injury via Suppression of Kidney Tissue Ras

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ravi Nistala ◽  
Javad Habibi ◽  
Annayya Aroor ◽  
Melvin R Hayden ◽  
Mona Garro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Renal Injury ◽  
Sodium Excretion ◽  
The United States ◽  
Western Diet ◽  
Ang Ii ◽  
High Fructose ◽  
Dppiv Inhibitor ◽  
And Oxidative Stress

Objectives: Obesity is an independent risk factor for development and progression of renal injury. High fructose corn syrup consumption has coincided with the obesity epidemic in the United States. High fructose (60%) diets have been demonstrated to be associated with elevation in BP and worsening insulin resistance along with renal injury via increased hepatic production of uric acid. Recently, DPPIV inhibitors have been shown to improve diabetic changes and sodium excretion, effects that are beyond glycemic control. Therefore, the renal protective benefits of DPPIV inhibition in a clinically relevant Western diet fed mouse model were examined. Methods: Mice fed a high fat/high fructose (WD) diet for 16 weeks and given a DPPIV inhibitor MK0626 in their diet were examined for metabolic parameters, inflammation, kidney renin-angiotensin system (RAS) and oxidative stress. Renal injury was assessed by biochemical, immunohistological and electron microscopy techniques. In vitro , angiotensin II (Ang II) effects on OKP-PTCs were assessed for mechanism. Results: MK0626 ameliorated WD-induced increases in serum uric acid, oxidative stress and RAS. WD induced suppression of IL-10 was reversed by MK0626. There was a tendency to improve HOMA-IR by MK0626 but no effect on BP and body weights. Diet induced DPPIV activation in the plasma and kidney of WD mice was abrogated by MK0626 (~80%). WD mice were characterized by increased proteinuria (~3-fold), mesangial expansion and podocyte effacement and these changes were prevented by MK0626. In addition, the PTC endocytosis protein megalin and basilar canalicular network and mitochondrial ultrastructure abnormalities were reversed by MK0626. WD mice had decreased sodium excretion which was improved by MK0626. Ang II directly increased DPPIV activity and sodium hydrogen exchanger activity in PTCs and decreased megalin protein, which was effectively prevented by MK0626. Conclusion: Thus, WD induced increases in DPPIV activity is associated with elevations in uric acid, renal RAS, inflammation and oxidative stress which may result in renal injury. These results suggest that DPPIV inhibitors prevent WD induced renal injury and offer a novel therapy for diabetic and obesity associated renal disease.

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

Effect of trimethylgallic acid esters against chronic stress-induced anxiety-like behavior and oxidative stress in mice

2014 ◽  
Vol 66 (4) ◽  
pp. 606-612 ◽  
Author(s):  
Mamta Sachdeva Dhingra ◽  
Sameer Dhingra ◽  
Rachna Kumria ◽  
Renu Chadha ◽  
Tejvir Singh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Stress ◽  
And Oxidative Stress ◽  
Acid Esters

scholarly journals Dimethyl fumarate protects nucleus pulposus cells from inflammation and oxidative stress and delays the intervertebral disc degeneration

2020 ◽  
Vol 20 (6) ◽  
pp. 1-1 ◽  
Author(s):  
Hainian Zhu ◽  
Gang Chen ◽  
Yuhua Wang ◽  
Xuchen Lin ◽  
Jingyuan Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Dimethyl Fumarate ◽  
Nucleus Pulposus Cells ◽  
And Oxidative Stress

scholarly journals Genomic Analysis ofSalmonella entericaSerovar Typhimurium Characterizes Strain Diversity for Recent U.S. Salmonellosis Cases and Identifies Mutations Linked to Loss of Fitness under Nitrosative and Oxidative Stress

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Hillary S. Hayden ◽  
Susana Matamouros ◽  
Kyle R. Hager ◽  
Mitchell J. Brittnacher ◽  
Laurence Rohmer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
United States ◽  
Genetic Factors ◽  
Inbred Mice ◽  
The United States ◽  
Sub Saharan Africa ◽  
Food Sources ◽  
Strain Diversity ◽  
Mexican Strains ◽  
And Oxidative Stress

ABSTRACTSalmonella entericaserovar Typhimurium is one of the most commonS. entericaserovars associated with U.S. foodborne outbreaks.S. Typhimurium bacteria isolated from humans exhibit wide-ranging virulence phenotypes in inbred mice, leading to speculation that some strains are more virulent in nature. However, it is unclear whether increased virulence in humans is related to organism characteristics or initial treatment failure due to antibiotic resistance. Strain diversity and genetic factors contributing to differential human pathogenicity remain poorly understood. We reconstructed phylogeny, resolved genetic population structure, determined gene content and nucleotide variants, and conducted targeted phenotyping assays forS. Typhimurium strains collected between 1946 and 2012 from humans and animals in the United States and abroad. Strains from recent U.S. salmonellosis cases were associated with fiveS. Typhimurium lineages distributed within three phylogenetic clades, which are not restricted by geography, year of acquisition, or host. Notably, two U.S. strains and four Mexican strains are more closely related to strains associated with human immunodeficiency virus (HIV)-infected individuals in sub-Saharan Africa than to other North American strains. Phenotyping studies linked variants specific to these strains inhmpAandkatEto loss of fitness under nitrosative and oxidative stress, respectively. These results suggest that U.S. salmonellosis is caused by diverseS. Typhimurium strains circulating worldwide. One lineage has mutations in genes affecting fitness related to innate immune system strategies for fighting pathogens and may be adapting to immunocompromised humans by a reduction in virulence capability, possibly due to a lack of selection for its maintenance as a result of the worldwide HIV epidemic.IMPORTANCENontyphoidalSalmonellabacteria cause an estimated 1.2 million illnesses annually in the United States, 80 million globally, due to ingestion of contaminated food or water.SalmonellaTyphimurium is one of the most common serovars associated with foodborne illness, causing self-limiting gastroenteritis and, in approximately 5% of infected patients, systemic infection. Although someS. Typhimurium strains are speculated to be more virulent than others, it is unknown how strain diversity and genetic factors contribute to differential human pathogenicity. Ours is the first study to examine the diversity ofS. Typhimurium associated with recent cases of U.S. salmonellosis and to provide some initial correlation between observed genotypes and phenotypes. Definition of specificS. Typhimurium lineages based on such phenotype/genotype correlations may identify strains with greater capability of associating with specific food sources, allowing outbreaks to be more quickly identified. Additionally, defining simple correlates of pathogenesis may have predictive value for patient outcome.

A Review on Mitochondrial Dysfunction and Oxidative stress due to Complex-Ⅰ in Parkinson Disease

2021 ◽  
pp. 167-170
Author(s):  
V Nuthan Kumar Babu ◽  
Navneet Khurana
Keyword(s):  
Oxidative Stress ◽  
Parkinson Disease ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorder ◽  
Dimethyl Fumarate ◽  
World Population ◽  
Emerging Therapies ◽  
And Oxidative Stress ◽  
Transplantation Therapy

Parkinson’s disease (PD) is the common physical movement disorder, and it is 2nd most progressive widespread neurodegenerative disorder all over the world, and it is reported that and essential 10 million, over 0.3 % of the total world population. A thoughtful reduction of the neurotransmitter dopamine (DA) in the striatum is the main cause of these motor symptoms, collectively known as parkinsonism. Mitochondria serves as most important organelle in most of the cells and are essential for life and it is also called as heart for all cellular metabolisms. The main and most important role of mitochondria is generation of ATP via oxidative phosphorylation. In this study will study about how complex Ⅰ deficiency effects the mitochondrial and oxidative stress and reactive oxygen species which cause mitochondrial dysfunction and we also study emerging therapies for Parkinson disease with the help of coenzyme Q10 and some genes like FUN-14, FUNDC-1 and dimethyl fumarate or BG-12 in some phases of clinical trials and also by cell transplantation therapy and in future this study helps in finding how this sporadic Parkinson disease occurs in parkinsonism.

Sign in / Sign up

Export Citation Format

Share Document