For study of antioxidant therapy efficiency in relapsing-remitting multiple
sclerosis we investigated group 1 (18 patients) treated with alpha-lipoic
acid and group 2 (14 patients) who received complex of antioxidants and
neuroprotectors with various mechanisms of action (oc-lipoic acid,
Nicotinamide, Acetylcysteine, Triovit Beta-carotine, Alpha-tocopheryl
acetate, Ascorbic acid, Selenium, Pentoxifylline, Cerebrolysin, Amantadine
hydrochloride) during 1 month, 2 times a year. The treatment resulted in
significant reduction (2-3 times) of relapse frequency in multiple sclerosis
patients (especially in group 2) and decrease of required corticosteroid
courses. After antioxidant therapy the content of lipid peroxide products
was significantly reduced (most expressed in group 2). The improved method
of multicomponent antioxidant and neuroprotective therapy can be considered
as pathogenic threatment in relapsing-remitting multiple sclerosis.


The role of oxidative stress in the pathogenesis of multiple sclerosis: the
need for effective antioxidant therapy.

Gilgun-Sherki Y, Melamed E, Offen D

J Neurol 2004 Mar 251:261-8

Abstract

Accumulating data indicate that oxidative stress (OS) plays a major role in
the pathogenesis of multiple sclerosis (MS). Reactive oxygen species (ROS),
leading to OS, generated in excess primarily by macrophages, have been
implicated as mediators of demyelination and axonal damage in both MS and
experimental autoimmune encephalomyelitis (EAE), its animal model. ROS cause
damage to cardinal cellular components such as lipids, proteins and nucleic
acids (e. g., RNA, DNA), resulting in cell death by necrosis or apoptosis.
In addition, weakened cellular antioxidant defense systems in the central
nervous system (CNS) in MS, and its vulnerability to ROS effects may
increase damage. Thus, treatment with antioxidants might theoretically
prevent propagation of tissue damage and improve both survival and
neurological outcome. Indeed, several experimental studies have been
performed to see whether dietary intake of several antioxidants prevents or
reduces the progression of EAE. Although a few antioxidants showed some
efficacy in these studies, little information is available on the effect of
treatments with such compounds in patients with MS. Well-designed clinical
studies using antioxidant intake, as well as investigations based on larger
cohorts studied over a longer periods of time, are needed in order to assess
whether antioxidant intake together with other conventional treatments,
might be beneficial in treating MS.

Author Address

Laboratory of Neurosciences, Felsenstein Medical Research Center, The
Sackler School of Medicine, Tel Aviv University, Petach Tikva 49100, Israel.


 Record 2

Flavonoids inhibit myelin phagocytosis by macrophages; a structure-activity
relationship study.

Hendriks JJ, de Vries HE, van der Pol SM, van den Berg TK, van Tol EA,
Dijkstra CD

Biochem Pharmacol 2003 Mar 65:877-85


Abstract

Demyelination is a characteristic hallmark of the neuro-inflammatory disease
multiple sclerosis. During demyelination, macrophages phagocytose myelin and
secrete inflammatory mediators that worsen the disease. Here, we
investigated whether flavonoids, naturally occurring immunomodulating
compounds, are able to influence myelin phagocytosis by macrophages in
vitro. The flavonoids luteolin, quercetin and fisetin most significantly
decreased the amount of myelin phagocytosed by a macrophage cell line
without affecting its viability. IC(50) values for these compounds ranged
from 20 to 80 microM. The flavonoid structure appeared to be essential for
observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4
positions in combination with a C-2,3 double bond were most effective. The
capacity of the various flavonoids to inhibit phagocytosis correlated well
with their potency as antioxidant, which is in line with the requirement of
reactive oxygen species for the phagocytosis of myelin by macrophages. Our
results implicate that flavonoids may be able to limit the demyelination
process during multiple sclerosis.

Author Address

Department of Molecular Cell Biology, VU Medical Centre, Van der
Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
jja.hendriks.cell@med.vu.nl

 Record 3

Vitamin E and neurodegenerative disorders associated with oxidative stress.

Butterfield DA, Castegna A, Drake J, Scapagnini G, Calabrese V

Nutr Neurosci 2002 Sep 5:229-39

Abstract

Several neurodegenerative disorders are associated with oxidative stress
that is manifested by lipid peroxidation, protein oxidation and other
markers. Included in these disorders in which oxidative stress is thought to
play an important role in their pathogenesis are Alzheimer's disease (AD),
Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), tardive
dyskinesia, Huntington's disease (HD), and multiple sclerosis. This review
presents some of the chemistry of vitamin E as an antioxidant and summarizes
studies in which vitamin E has been employed in these disorders and models
thereof.

Author Address

Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown
Center on Aging, University of Kentucky, Lexington 40506, USA.
dabcns@uky.edu


 Record 4

Serum levels of antioxidant vitamins and lipid peroxidation in multiple
sclerosis.

Besler HT, Comog˜lu S, Okçu Z

Nutr Neurosci 2002 Jun 5:215-20

Abstract

We determined serum levels of ascorbic acid, betacarotene, retinol and alpha
tocopherol and lipid peroxidation (as estimated by thiobarbituric acid
reacting substances (TBARS) generation) in 24 multiple sclerosis (MS)
patients and 24 healthy sex- and age-matched person as control. The levels
of four antioxidant vitamins were significantly lower in MS patients
compared to controls (p < 0.05). TBARS levels were significantly higher in
the patients of MS compared to the controls (p = 0.001). In MS patients, the
levels of beta-carotene, alpha tocopherol and ascorbic acid correlated
significantly with each other (r2 = 0.689 - 0.779). It appeared that there
was inverse correlation between the serum levels of ascorbic acid or
beta-carotene, but not of alpha tocopherol or retinol, and TBARS levels in
MS. The present study indicates that antioxidant vitamins (alpha tocopherol,
beta-carotene, retinol and ascorbic acid) are decreased in sera of MS
patients during an attack, and that this decrease may well be dependent on
the increased oxidative burden as reflected by lipid peroxidation products.
The role of antioxidant vitamin supplementation in prevention and/or
treatment of MS remains to be explored.

Author Address

Department of Nutrition and Dietetics, School of Health Technology,
Hacettepe University, Sihhiye, Ankara, Turkey. htbf@hacettepe.edu.tr


 Record 7

Oxidative stress in patients with multiple sclerosis.

Syburra C, Passi S

Ukr Biokhim Zh 1999 May-Jun 71:112-5


Abstract

It is well known that brain and nervous system cells are prone to oxidative
damage because of their relatively low content of antioxidants, especially
enzymatic ones, and of the high levels of both membrane polyunsaturated
fatty acids (PUFA) and iron easily released from injured cells. We have
investigated the oxidative stress in the blood (plasma, erythrocytes and
lymphocytes) of 28 patients affected with multiple sclerosis (MS) and of 30
healthy age matched controls, by performing a multiparameter analysis of
non-enzymatic and enzymatic antioxidants--Vitamin E (Vit. E), ubiquinone
(UBI), reduced and oxidized glutathione (GSH, GS-SG), superoxide dismutase
(SOD), glutathione peroxidase (GPX), catalase (CAT) and fatty acid patterns
of phospholipids (PL-FA). PL-FA and Vit. E were assayed by GC-MS; UBI and
GSH/GS-SG by HPLC; SOD, GPX and CAT by spectrophotometry. In comparison to
controls, patients with MS showed significantly reduced levels of plasma UBI
(0.21 ± 0.10 vs. 0.78 ± 0.08 mg/ml, p < 0.001), plasma Vit. E (7.4 ±
2.1 vs. 11.4 ± 1.8 mg/ml, p < 0.01), lymphocyte UBI (8.1 ± 4.0 vs. 30.3
± 7.2 ng/ml blood, p < 0.001) and erythrocyte GPX (22.6 ± 5.7 vs. 36.3
± 6.4 U/g Hb, p < 0.001). This blood antioxidant deficiency was associated
with plasma levels of PL-PUFA--especially C20:3 n-6 and C20:4
n-6--significantly higher than controls. In conclusion, the blood of
patients with MS shows the signs of a significant oxidative stress. The
possibility of counteracting it by antioxidant administration plus an
appropriate diet, might represent a promising way of inhibiting the
progression of the disease. Antioxidant supplements should include not only
GSH repleting agents, but also Vit. E, ubiquinol, and selenium.



MeSH

Adult; Antioxidants; Case-Control Studies; Chromatography, High Pressure
Liquid; Fatty Acids; Human; Middle Aged; Multiple Sclerosis; Oxidative
Stress; Phospholipids; Spectrum Analysis; Support, Non-U.S. Gov't
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