Extra-Virgin Olive Oil Modifies the Changes Induced in Non-Nervous Organs and Tissues by Experimental Autoimmune Encephalomyelitis Models.

This study reveals the existence of oxidative stress (reactive oxygen species (ROS)) in non-nervous organs and tissues in multiple sclerosis (MS) by means of a model of experimental autoimmune encephalomyelitis (EAE) in rats. This model reproduces a similar situation to MS, as well as its relationship with intestinal microbiota starting from the changes in bacterial lipopolysaccharide levels (LPS) in the outer wall of the gram-negative bacteria. Finally, the administration of extra-virgin olive oil (EVOO), hydroxytirosol (HT), and oleic acid (OA) exert beneficial effects. Twenty-five Dark Agouti two-month-old male rats, weighing around 190 g, were distributed into the following groups: Control, EAE (experimental autoimmune encephalomyelitis group), EAE + EVOO, EAE + HT, and EAE + OA. The glutathione redox system with the EAE was measured in heart, kidney, liver, and small and large intestines. The LPS and the correlation with oxidative stress in the small and large intestines were also investigated. The results showed that (1) the oxidative damage in the EAE model affects non-nervous organs and tissues; (2) The LPS is related to inflammatory phenomena and oxidative stress in the intestinal tissue and in other organs; (3) The administration of EVOO, HT, and OA reduces the LPS levels at the same time as minimizing the oxidative damage; (4) EVOO, HT, and OA improve the disease's clinical score; and (5) on balance, EVOO offers a better neuroprotective effect.

Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis Model.

Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord. For this purpose, samples obtained from EAE rats and relapsing-remitting (RRMS) MS patients were used. In addition, EAE rats were treated with Natalizumab, N-acetyl-cysteine and dimethyl fumarate. Natalizumab was also employed in RRMS. The results of this study revealed an improvement in the clinical symptoms of the EAE and MS with the treatments, as well as a reduction in the oxidative stress parameters and in LBP. Correlations between the clinical variables of the disease, i.e. oxidative damage and LBP, were established. Although the conclusions of this research are indeed relevant, further investigation would be necessary to establish the intrinsic mechanisms of the MS-oxidative stress-microbiota relationship.

Natalizumab Modifies Catecholamines Levels Present in Patients with Relapsing- Remitting Multiple Sclerosis.

AIMS: The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS. METHODS: For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG). RESULTS: The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group. CONCLUSION: Natalizumab normalizes altered melatonin and norepinephrine levels in MS.

Skeletal muscle findings in experimental autoimmune encephalomyelitis.

INTRODUCTION: Skeletal muscle is a target organ in multiple sclerosis, a chronic debilitating disease of the central nervous system caused by demyelination and axonal deterioration. Since the experimental autoimmune encephalomyelitis model reproduces the relapsing-remitting course found in most multiple sclerosis patients, this model was used to compare the histological features of skeletal muscle at onset with those observed at the start of the second relapse. MATERIAL AND METHODS: Histological, histochemical and ultrastructural changes, as well as biochemical oxidative damage and antioxidant-system markers, were examined in the soleus and extensor digitorum longus muscles of Dark Agouti rats in which experimental autoimmune encephalomyelitis had been induced by active immunization using myelin oligodendrocyte glycoprotein. RESULTS: Histological examination at disease onset revealed ragged-red fibers and ultrastructural evidence of mitochondrial degeneration. At the second relapse, neurogenic changes included a wide range of cytoarchitectural lesions, skeletal muscle atrophy and the appearance of intermediate fibers; however, differences were observed between soleus and extensor digitorum longus lesions. Biochemical tests disclosed an increase in oxidative stress markers at onset, which was more pronounced at the second relapse. CONCLUSIONS: Microscopic findings suggest that two patterns can be distinguished at disease onset: an initial phase characterized by muscle mitochondrial alterations, and a second phase dominated by a histological muscle pattern of clearly neurogenic origin.

Elevated melatonin levels in natalizumab-treated female patients with relapsing-remitting multiple sclerosis: relationship to oxidative stress.

Natalizumab is currently the most successful clinical treatment for multiple sclerosis. The use of this drug is associated with the reduction in the number of relapses and a slowing in disease progression, as well as an improvement in signs and symptoms displayed by the patients. To evaluate the effect of natalizumab on melatonin and its relationship with peripheral oxidative damage, we studied the serum melatonin levels in 18 patients with relapsing-remitting multiple sclerosis. Natalizumab caused significant increases in serum melatonin concentrations. This change was associated with a rise in increase of antioxidants and a reduction in oxidative stress biomarkers. In conclusion, these data may explain, at least in part, some of the beneficial effects exhibited by disease antibody such as its antioxidant capacity.

Effect of natalizumab on oxidative damage biomarkers in relapsing-remitting multiple sclerosis.

BACKGROUND: Natalizumab is a monoclonal antibody used to treat multiple sclerosis. This study sought to determine whether the protective action of natalizumab involved a reduction in oxidative damage. METHODS: Twenty-two multiple sclerosis patients fulfilling the revised McDonald criteria were assigned to treatment with 300 mg natalizumab intravenously once monthly (infusion every 4 weeks) in accordance with Spanish guidelines. Carbonylated proteins, 8-hydroxy-2'-deoxyguanosine, total glutathione, reduced glutathione, superoxide dismutase, glutathione peroxidase, and myeloperoxidase levels were measured at baseline and after 14 months' treatment, and the antioxidant gap was calculated. RESULTS: Natalizumab prompted a drop in oxidative-damage biomarker levels, together with a reduction both in myeloperoxidase levels and in the myeloperoxidase/neutrophil granulocyte ratio. Interestingly, natalizumab induced nuclear translocation of Nrf2 and a fall in serum vascular cell adhesion molecule-1 levels. CONCLUSION: These findings suggest that natalizumab has a beneficial effect on oxidative damage found in MS patients.