A Review of Various Antioxidant Compounds and their Potential Utility as Complementary Therapy in Multiple Sclerosis

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS). The etiology of this multifactorial disease has not been clearly defined. Conventional medical treatment of MS has progressed, but is still based on symptomatic treatment. One of the key factors in the pathogenesis of MS is oxidative stress, enhancing inflammation and neurodegeneration. In MS, both reactive oxygen and nitrogen species are formed in the CNS mainly by activated macrophages and microglia structures, which can lead to demyelination and axon disruption. The course of MS is associated with the secretion of many inflammatory and oxidative stress mediators, including cytokines (IL-1b, IL-6, IL-17, TNF-α, INF-γ) and chemokines (MIP-1a, MCP-1, IP10). The early stage of MS (RRMS) lasts about 10 years, and is dominated by inflammatory processes, whereas the chronic stage is associated with neurodegenerative axon and neuron loss. Since oxidative damage has been known to be involved in inflammatory and autoimmune-mediated processes, antioxidant therapy could contribute to the reduction or even prevention of the progression of MS. Further research is needed in order to establish new aims for novel treatment and provide possible benefits to MS patients. The present review examines the roles of oxidative stress and non-pharmacological anti-oxidative therapies in MS.

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1973834 ◽

2016 ◽

Vol 2016 ◽

pp. 1-18 ◽

Cited By ~ 44

Author(s):

Bożena Adamczyk ◽

Monika Adamczyk-Sowa

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Chronic Phase ◽

Current Treatment ◽

New Drugs ◽

Inflammatory Processes ◽

The Central Nervous System ◽

The Brain ◽

Methods Of Treatment

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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An association study of two functional promotor polymorphisms in the myeloperoxidase (MPO) gene in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458506075315 ◽

2007 ◽

Vol 13 (6) ◽

pp. 697-700 ◽

Cited By ~ 6

Author(s):

F. Lundmark ◽

H. Salter ◽

J. Hillert

Keyword(s):

Multiple Sclerosis ◽

Complex Disease ◽

Control Material ◽

Gene Encoding ◽

Immunological Responses ◽

Inflammatory Processes ◽

The Central Nervous System ◽

Genetic And Environmental Factors ◽

Large Case

Multiple sclerosis (MS) is a chronic neurological disease affecting the central nervous system (CNS). The disease is characterised by demyelination and axonal loss caused by abnormal immunological responses resulting in accumulating neurological disabilities. MS is considered a complex disease, with both genetic and environmental factors contributing to the pathogenesis. In this study, we have investigated the genetic role of the myeloperoxidase (MPO) gene encoding myeloperoxidase in MS. MPO is an enzyme found in myeloid cells which catalyses the production of hypochlorus acid, a potent microbicidal agent. It also plays an important role in inflammatory processes, where migrating neutrophiles may release active MPO and cause tissue damage. In this study, we investigated two polymorphisms located in the promotor region of the MPO gene, known to influence the expression of MPO, in a large case/control material consisting of 871 Swedish MS patients and 532 Swedish healthy controls. No association was observed with risk of MS. Multiple Sclerosis 2007; 13: 697-700. http://msj.sagepub.com

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Multiple Sclerosis Biomarker Discoveries by Proteomics and Metabolomics Approaches

Biomarker Insights ◽

10.1177/11772719211013352 ◽

2021 ◽

Vol 16 ◽

pp. 117727192110133

Author(s):

Ameneh Jafari ◽

Amirhesam Babajani ◽

Mostafa Rezaei-Tavirani

Keyword(s):

Multiple Sclerosis ◽

Complex Disease ◽

Biomarker Discovery ◽

Response To Treatment ◽

Inflammatory Disorder ◽

Protein Marker ◽

Complex Disorders ◽

New Information ◽

The Central Nervous System ◽

Monitoring Treatment

Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system (CNS) resulting in demyelination and axonal loss in the brain and spinal cord. The precise pathogenesis and etiology of this complex disease are still a mystery. Despite many studies that have been aimed to identify biomarkers, no protein marker has yet been approved for MS. There is urgently needed for biomarkers, which could clarify pathology, monitor disease progression, response to treatment, and prognosis in MS. Proteomics and metabolomics analysis are powerful tools to identify putative and novel candidate biomarkers. Different human compartments analysis using proteomics, metabolomics, and bioinformatics approaches has generated new information for further clarification of MS pathology, elucidating the mechanisms of the disease, finding new targets, and monitoring treatment response. Overall, omics approaches can develop different therapeutic and diagnostic aspects of complex disorders such as multiple sclerosis, from biomarker discovery to personalized medicine.

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HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population

Multiple Sclerosis Journal ◽

10.1177/1352458510376177 ◽

2010 ◽

Vol 16 (10) ◽

pp. 1173-1177 ◽

Cited By ~ 10

Author(s):

M. Shahbazi ◽

H. Ebadi ◽

D. Fathi ◽

D. Roshandel ◽

M. Mohamadhosseni ◽

...

Keyword(s):

Multiple Sclerosis ◽

Central Nervous System ◽

Nervous System ◽

Promoter Polymorphism ◽

Exact Test ◽

Inflammatory Processes ◽

The Central Nervous System ◽

Pcr Method ◽

Multiple Sclerosis Patients ◽

The Impact

Background: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis. Objective: To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects. Method: The SSP-PCR method was used to determine genotypes and Fisher’s exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2—2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1—1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5—2.5, p < 0.0001). Results: Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501. Conclusions: We suggest more studies to confirm these results in other populations.

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

Clinical and Developmental Immunology ◽

10.1155/2013/708659 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 86

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.

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The Role of Fampridine in the Symptomatic Treatment of Gait Impairment in Patients with Multiple Sclerosis

Acta Balneologica ◽

10.36740/abal201903108 ◽

2019 ◽

Vol 61 (3) ◽

pp. 199-207

Author(s):

Michał Piwoński ◽

Klaudia Żak ◽

Patrycja Gierszon ◽

Izabela Morawska ◽

Dominika Psiuk ◽

...

Keyword(s):

Multiple Sclerosis ◽

English Language ◽

Demyelinating Disease ◽

Symptomatic Treatment ◽

Gait Pattern ◽

Modern Medicine ◽

Gait Impairment ◽

Slowing Down ◽

The Central Nervous System ◽

Short Time

Introduction: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system, the treatment of which remains a great challenge for modern medicine. An important part of it, apart from the treatment slowing down the process of demyelination, is the symptomatic treatment of sphincteral disorders, spasticity, muscle weakness, visual disturbances, mood, depression and gait impairment, which have been carried out with the use of fampridine for a short time. Materials and Methods: The study uses the method of literature analysis in the form of full English-language articles available in the PubMed and Google Scholar database describing the assessment of the effectiveness of fampridine in the symptomatic treatment of gait impairment in MS patients. Results: In each of the studies cited, the ability to walk is indicated in patients taking fampridine compared to placebo. An improvement in walking speed, distance and physical activity is observed. The gait pattern changes. In addition, there is a lack of efficacy of 5 mg dalfampridine ER, with a significant effect on the dose rate of 10 mg. After 2 weeks of discontinuation, the improvement is reversed. Conclusion: A significant effect of fampridine in a dose of 10 mg on improvement of walking in patients with MS is observed. However, it seems necessary for the therapy to be carried out without interruption.

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Engine Failure in Axo-Myelinic Signaling: A Potential Key Player in the Pathogenesis of Multiple Sclerosis

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.610295 ◽

2021 ◽

Vol 15 ◽

Author(s):

Talia Bergaglio ◽

Antonio Luchicchi ◽

Geert J. Schenk

Keyword(s):

Multiple Sclerosis ◽

Tissue Injury ◽

Neuronal Loss ◽

Glia Cells ◽

Inflammatory Processes ◽

The Central Nervous System ◽

Triggering Mechanisms ◽

Engine Failure ◽

Inside Out ◽

Ms Pathogenesis

Multiple Sclerosis (MS) is a complex and chronic disease of the central nervous system (CNS), characterized by both degenerative and inflammatory processes leading to axonal damage, demyelination, and neuronal loss. In the last decade, the traditional outside-in standpoint on MS pathogenesis, which identifies a primary autoimmune inflammatory etiology, has been challenged by a complementary inside-out theory. By focusing on the degenerative processes of MS, the axo-myelinic system may reveal new insights into the disease triggering mechanisms. Oxidative stress (OS) has been widely described as one of the means driving tissue injury in neurodegenerative disorders, including MS. Axonal mitochondria constitute the main energy source for electrically active axons and neurons and are largely vulnerable to oxidative injury. Consequently, axonal mitochondrial dysfunction might impair efficient axo-glial communication, which could, in turn, affect axonal integrity and the maintenance of axonal, neuronal, and synaptic signaling. In this review article, we argue that OS-derived mitochondrial impairment may underline the dysfunctional relationship between axons and their supportive glia cells, specifically oligodendrocytes and that this mechanism is implicated in the development of a primary cytodegeneration and a secondary pro-inflammatory response (inside-out), which in turn, together with a variably primed host’s immune system, may lead to the onset of MS and its different subtypes.

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Oxidative Stress and Neuroinflammation Potentiate Each Other to Promote Progression of Dopamine Neurodegeneration

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/6137521 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Jingyi He ◽

Guofu Zhu ◽

Guoqing Wang ◽

Feng Zhang

Keyword(s):

Oxidative Stress ◽

Complex Disease ◽

Lewy Bodies ◽

Oxygen Species ◽

Independent Factor ◽

Internal Environment ◽

Progressive Loss ◽

Entry Points ◽

Toxic Environment ◽

The Central Nervous System

Parkinson’s disease (PD) is a chronic and complex disease of the central nervous system (CNS). Progressive loss of dopamine (DA) neurons in midbrain substantia nigra is considered to be the main cause of PD. The hallmark of PD pathology is the formation of Lewy bodies and the deposition of α-synuclein (α-syn). The mechanisms responsible for the progressive feature of DA neurodegeneration are not fully illustrated. Recently, oxidative stress and neuroinflammation have received extensive attention as two important entry points in the pathogenesis of PD. The occurrence of oxidative stress and neuroinflammation is usually derived from external influences or changes in internal environment, such as the accumulation of reactive oxygen species, exposure to a toxic environment, and the transformation of systemic inflammation. However, PD never results from a single independent factor and the simultaneous participation of oxidative stress and neuroinflammation contributed to PD development. Oxidative stress and neuroinflammation could potentiate each other to promote progression of PD. In this review, we briefly summarized the conditions of oxidative stress and neuroinflammation and the crosstalk between oxidative stress and neuroinflammation on the development of PD.

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Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity

Multiple Sclerosis Journal ◽

10.1191/1352458505ms1240oa ◽

2005 ◽

Vol 11 (6) ◽

pp. 677-682 ◽

Cited By ~ 85

Author(s):

G Ferretti ◽

T Bacchetti ◽

F Principi ◽

F Di Ludovico ◽

B Viti ◽

...

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Cholesteryl Ester ◽

Early Stage ◽

Biologically Active ◽

Plasma Lipoproteins ◽

High Density Lipoproteins ◽

Lipid Hydroperoxides ◽

Paraoxonase Activity ◽

Anti Oxidant

Paraoxonase, an enzyme associated with high density lipoproteins (HDL), plays an important role in the anti-oxidant and anti-inflammatory properties exerted by HDL. Increasing evidence supports a role of free radicals and oxidative stress in the inflammatory processes and in the pathogenesis of multiple sclerosis (MS). The aim of this study was to further investigate the relationship between oxidative damage and MS; therefore we compared the paraoxonase activity and levels of cholesteryl ester hydroperoxides (CE-OOH), as marker of lipid peroxidation, in plasma isolated from healthy subjects (n=89) and from MS patients (n=24) in the early stage disability (EDSSB<3.5). Our results demonstrated for the first time that the activity of paraoxonase in the plasma of MS subjects was significantly lower with respect to controls (p<0.001). Moreover, our results showed a significant increase in the levels of CE-OOH in plasma from MS subjects (p<0.001). CE-OOH are biologically active substances derived from the oxidation of cholesteryl ester localized in the hydrophobic core of plasma lipoproteins (HDL, LDL). Therefore, our study demonstrates alterations of lipoprotein peroxidation in MS and provides further evidence that oxidative stress and impairment of the anti-oxidant system may play a role in MS.

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Pathology and Pathogenesis of Progressive Multiple Sclerosis: Concepts and Controversies

Neurology International Open ◽

10.1055/s-0043-106704 ◽

2017 ◽

Vol 01 (03) ◽

pp. E171-E181

Author(s):

Adrian-Minh Schumacher ◽

Christoph Mahler ◽

Martin Kerschensteiner

Keyword(s):

Multiple Sclerosis ◽

Cognitive Deficits ◽

Progressive Disease ◽

Disease Duration ◽

Disease Process ◽

Progressive Multiple Sclerosis ◽

Relapsing Remitting ◽

Inflammatory Processes ◽

The Central Nervous System

AbstractMultiple sclerosis (MS) is an inflammatory disease of the central nervous system that initially is often dominated by relapsing-remitting neurological symptoms. With increasing disease duration these relapses are more and more superimposed by a progressive disease process that leads to an irreversible accumulation of motor, sensory and cognitive deficits. This progressive phase of MS is still only incompletely understood and by and large refractory to therapy. Here we aim to use recent pathological and pathomechanistic insights to outline a unifying concept of progressive MS. Based on this view of the disease we examine current controversies surrounding progressive MS. We discuss whether neurodegenerative or inflammatory processes drive progression, question whether the classification of primary and secondary progressive MS is all that useful and deliberate, which therapeutic strategies are best suited to limit the insidious neurological decline of progressive MS patients.

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