The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat.

This study has evaluated the effect of EVOO (Extra-Virgin olive oil), OA (oleic acid) and HT (hydroxytyrosol) in an induced model of MS through experimental autoimmune encephalomyelitis (EAE).Dark Agouti 2-month old rats (25 males) were divided into five groups: (i) control group, (ii) EAE group, (iii) EAE+EVOO, (iv) EAE+HT, and (v) EAE+OA. At 65 days, the animals were sacrificed and the glutathione redox system and bacterial lipopolysaccharide (LPS) and LPS-binding protein (LBP) products of the microbiota in brain, spinal cord, and blood were evaluated.Gastric administration of EVOO, OA, and HT reduced the degree of lipid and protein oxidation, and increased glutathione peroxidase, making it a diet-based mechanism for enhancing protection against oxidative damage. In addition, it reduced the levels of LPS and LBP, which appeared as being increased in the EAE correlated with the oxidative stress produced by the disease.

Dose-dependent S-allyl cysteine ameliorates multiple sclerosis disease-related pathology by reducing oxidative stress and biomarkers of dysbiosis in experimental autoimmune encephalomyelitis.

Garlic is a component of the Mediterranean diet. S-allyl cysteine (SAC), the most common organosulphur present in garlic, possesses neuroprotective properties. This investigation was performed to evaluate the dose-dependent protective action of SAC on oxidative damage, inflammation and gut microbiota alterations biomarkers. Experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis (MS) was induced by the myelin oligodendrocyte glycoprotein (MOG), whose effects were quantified by examining the changes in: clinical score, lipid peroxidation products, carbonylated proteins, glutathione system, tumor necrosis factor alpha (TNFα), and lipopolysaccharide membrane bacteria (LPS). Our results reveal that MOG induces paralysis, oxidative damage and increases in LPS binding protein (LBP) and LPS levels. In this work, two doses of SAC were compared with two dose of N-acetyl cysteine (NAC). SAC was more effective than NAC and it prevented the harmful effects induced by MOG more effectively at the dose of 50mg/kg than that of 18mg/kg. Surprisingly, NAC increases LBP levels while SAC had not such negative effect. In conclusion the data show the ability of SAC to modify EAE evolution.

Transcranial magnetic stimulation and aging: Effects on spatial learning and memory after sleep deprivation in Octodon degus.

The benefits of neuromodulatory procedures as a possible therapeutic application for cognitive rehabilitation have increased with the progress made in non-invasive modes of brain stimulation in aged-related disorders. Transcranial magnetic stimulation (TMS) is a non-invasive method used to examine multiple facets of the human brain and to ameliorate the impairment in cognition caused by Alzheimer's disease (AD). The present study was designed to evaluate how a chronic TMS treatment could improve learning and memory functions after sleep deprivation (SD) in old Octodon degus. SD was executed by gently handling to keep the animals awake throughout the night. Thirty young and twenty-four old O. degus females were divided in six groups (control, acute and chronic TMS treatment). Behavioral tests included; Radial Arm Maze (RAM), Barnes Maze (BM) and Novel Object Recognition (NOR). Although learning and memory functions improved in young animals with only one session of TMS treatment, a significant improvement in cognitive performance was seen in old animals after 4 and 7days of TMS, depending on the task that was performed. No side effects were observed following, which showed therapeutic potential for improving age-related cognitive performance.

Cognitive Impairment After Sleep Deprivation Rescued by Transcranial Magnetic Stimulation Application in Octodon degus.

Sleep is indispensable for maintaining regular daily life activities and is of fundamental physiological importance for cognitive performance. Sleep deprivation (SD) may affect learning capacity and the ability to form new memories, particularly with regard to hippocampus-dependent tasks. Transcranial magnetic stimulation (TMS) is a non-invasive procedure of electromagnetic induction that generates electric currents, activating nearby nerve cells in the stimulated cortical area. Several studies have looked into the potential therapeutic use of TMS. The present study was designed to evaluate how TMS could improve learning and memory functions following SD in Octodon degus. Thirty juvenile (18 months old) females were divided into three groups (control, acute, and chronic TMS treatment-with and without SD). TMS-treated groups were placed in plastic cylindrical cages designed to keep them immobile, while receiving head magnetic stimulation. SD was achieved by gently handling the animals to keep them awake during the night. Behavioral tests included radial arm maze (RAM), Barnes maze (BM), and novel object recognition. When TMS treatment was applied over several days, there was significant improvement of cognitive performance after SD, with no side effects. A single TMS session reduced the number of errors for the RAM test and improved latency and reduced errors for the BM test, which both evaluate spatial memory. Moreover, chronic TMS treatment brings about a significant improvement in both spatial and working memories.

Prepubertal children with suitable fitness and physical activity present reduced risk of oxidative stress.

To assess the impact of fitness status and physical activity on oxidative stress in prepubertal children, we measured selected biomarkers such as protein carbonyls (PC), lipid peroxidation products, and total nitrites, as well as the antioxidant system: total glutathione (TG), oxidized glutathione (GSSG), reduced glutathione (GSH), superoxide dismutase activity, and glutathione peroxidase. A total of 132 healthy children ages 7-12, at prepubertal stage, were classified into two groups according to their fitness level: low fitness (LF) and high fitness (HF). They were observed while engaged in an after-school exercise program, and a questionnaire was created to obtain information on their physical activity or sedentary habits. Plasma and red blood cells were obtained to analyze biomarkers. Regarding oxidative stress markers, the LF group and the sedentary group showed higher levels of TG and GSSG and a lower GSH/GSSG ratio than the HF group and the children engaged in physical activity. A negative association was found between PC and GSSG and TG and between TG and the GSH/GSSG ratio. Moreover, a negative correlation was found between GSSG and fitness, with a positive correlation with the GSH/GSSG ratio. TG, GSSG, and the GSH/GSSG ratio seem to be reliable markers of oxidative stress in healthy prepubertal children with low fitness or sedentary habits. This research contributes to the recognition that an adequate level of fitness and recreational physical activity in childhood leads to better health and oxidative status.

[Natalizumab and reduction of carbonylated proteins in patients with multiple sclerosis]. / Natalizumab y reduccion de los niveles de proteinas carboniladas en pacientes con esclerosis multiple.

INTRODUCTION: The sensitivity of the central nervous system to oxidative damage and its relationship with inflammatory response are well known. Recent studies have shown that oxidative stress is present in the establishment and development of multiple sclerosis (MS). One of the most recent treatments in this process is natalizumab, a monoclonal antibody. AIM: To evaluate whether the therapeutic effect of natalizumab is associated with the severity of the disease and the oxidative damage. PATIENTS AND METHODS: Researchers recruited twenty patients with relapsing-remitting MS (RRMS) undergoing therapy with natalizumab and distributed, according to the Expanded Disability Status Scale (EDSS), in two groups: RRMS-1 (EDSS < 5) and RRMS-2 (EDSS ≥ 5). Blood samples were taken for an oxidative profile study. RESULTS: Data showed a decrease in carbonylated proteins following treatment with natalizumab. The reduction in oxidative damage rated as protein oxidation is significant between the previous (baseline) situation of the patient and after 14 months' treatment. The most significant decrease coincided with the patients with the highest levels of severity in the process. Although it has not been possible to establish a correlation, the statistical significance is higher for patients in the RRMS-2 group treated with natalizumab. The antioxidant systems, on the other hand, did not display any statistically significant changes. CONCLUSIONS: Natalizumab brings about a reduction in carbonylated protein levels.

Neuroprotective effects of extremely low-frequency electromagnetic fields on a Huntington's disease rat model: effects on neurotrophic factors and neuronal density.

There is evidence to suggest that the neuroprotective effect of exposure of extremely low-frequency electromagnetic fields (ELF-EMF) may be due, at least in part, to the effect of these fields on neurotrophic factors levels and cell survival, leading to an improvement in behavior. This study was undertaken to investigate the neuroprotective effects of ELFEF in a rat model of 3-nitropropionic acid (3NP)-induced Huntington's disease. Behavior patterns were evaluated, and changes in neurotrophic factor, cell damage, and oxidative stress biomarker levels were monitored in Wistar rats. Rats were given 3NP over four consecutive days (20 mg/kg body weight), whereas ELFEF (60 Hz and 0.7 mT) was applied over 21 days, starting after the last injection of 3NP. Rats treated with 3NP exhibited significantly different behavior in the open field test (OFT) and the forced swim test (FST), and displayed significant differences in neurotrophic factor levels and oxidative stress biomarkers levels, together with a neuronal damage and diminished neuronal density, with respect neuronal controls. ELFEF improved neurological scores, enhanced neurotrophic factor levels, and reduced both oxidative damage and neuronal loss in 3NP-treated rats. ELFEF alleviates 3NP-induced brain injury and prevents loss of neurons in rat striatum, thus showing considerable potential as a therapeutic tool.

Olive oil reduces oxidative damage in a 3-nitropropionic acid-induced Huntington's disease-like rat model.

Free radicals contribute to altered neuronal functions in neurodegenerative diseases and brain aging, by producing lipid- and other molecule-dependent modifications. The Mediterranean diet has been associated with a reduced risk of neurodegenerative disease. This study sought to verify whether extra-virgin olive oil (EVOO) exerted a brain antioxidant effect, protecting the brain against the oxidative stress caused by 3-nitropropionic acid (3NP). 3NP was administered intraperitoneally (i.p.) at a dose of 20 mg/kg body weight over four consecutive days. EVOO (representing 10% of calorie intake in the total standard daily diet of rats) and hydroxytyrosol (HT; 2.5 mg/kg body weight) were administered for 14 days. In all studied samples, 3NP caused a rise in lipid peroxides (LPO) and a reduction in glutathione (GSH) content. While the results showed that EVOO and HT reduces lipid peroxidation product levels and blocks the GSH depletion prompted by 3NP in both striatum and rest of the brain in Wistar rats. In addition, EVOO blocks and reverses the effect of 3NP on succinate dehydrogenase activity. In brief, the data obtained indicate that EVOO and HT act as a powerful brain antioxidant.

Cardiorespiratory fitness and oxidative stress: effect of acute maximal aerobic exercise in children and adolescents.

AIM: Evaluate the effects of oxidative stress in saliva in young males, according to their cardiorespiratory fitness and taking acute maximal aerobic exercise into consideration. An incremental exercise test (20 meter shuttle run) was used. METHODS: Seventy healthy male subjects, aged 10 to 14 years, were included in the study and were classified into two groups according to fitness parameters. Subjects were expected to take the 20 meter shuttle run test. RESULTS: Group I had high cardiorespiratory fitness while group II had low cardiorespiratory fitness below the mean for their age. Saliva samples were taken before and immediately after exercise in order to measure levels of reduced glutathione, lipoperoxides, glutathione/lipoperoxides ratio and catalase. The values of reduced glutathione were significantly diminished regardless the subjects' cardiorespiratory fitness. The glutathione/lipoperoxides ratio was significantly diminished in group I. In addition, positive correlations were observed between lipoperoxides values after the 20 meter shuttle run test. CONCLUSION: High cardiorespiratory fitness does not seem to be an essential factor effecting in the oxidative stress values before exercise. However, oxidative stress could be greater with more intensity and duration after and acute maximal physical exercise.

Mice lacking the peroxisome proliferator-activated receptor α gene present reduced number of dopamine neurons in the substantia nigra without altering motor behavior or dopamine neuron decline over life.

Peroxisome proliferator-activated receptor alpha (PPAR-α), which is expressed by neurons of the nigrostriatal circuit, plays a prominent role in oxidative stress and neuroinflammation. The objectives were: (i) to discern if levels of antioxidant molecules and pro-inflammatory cytokines, along with PPAR-γ expression are modified in the nigrostriatal region of null PPAR-α mice, (ii) to discern whether dopaminergic neuronal features of the substantia nigra pars compacta (SNpc) and dorsal striatum are affected in null mice, and (iii) to establish if aging-induced decline of nigral neurons is different in null PPAR-α mice relative to wild-type littermates. A substantial decrease in antioxidant molecules was found in SNpc of null mice, by using ELISA. The pro-inflammatory factors TNF-α and IL-3 were found to be reduced in the substantia nigra, suggesting dual and opposite effects of PPAR-α deficiency on oxidative and pro-inflammatory molecules. Immunohistological and stereological studies revealed that young null mice present a smaller SNpc (-19.8%; TH downregulation was discarded). Normal locomotion in an open-field was not affected in null mice. Dopamine cell death could be caused by reduced protection against oxidative stress. Old null mice showed a percentage reduction of nigral dopamine neurons similar to that of young null animals, with a rate of decline over life of around 44%, the same value than that of wild-type littermates. These findings suggest that nuclear PPAR-α is necessary for the normal development of the substantia nigra along with normal levels of antioxidant molecules. Lack of PPAR-α does not modify the normal motor behavior of mice or decline of nigral dopamine neurons throughout life.

Huntingtons Disease: The Value of Transcranial Meganetic Stimulation

Huntington's disease (HD) is a genetic neurodegenerative process whose etiology is based on a localized disturbance in the short arm of chromosome 4 that encodes the huntingtin protein (Htt). The elongation of triple CAG for glutamine characterizes this change. Mutated Htt (mHtt) causes the appearance of intracellular aggregates inducing alterations in mitochondrial metabolism in the form of reactive oxygen species (ROS) and ATP depletion. The oxidative imbalance caused by mHtt leads the neurons to a state of oxidative stress resulting in damage to macromolecules and cellular death. Since the discovery of certain mechanisms underlying the pathogenesis of HD, several therapeutic procedures have been shown to delay or slow the evolution of the condition and have demonstrated the biochemical and molecular mechanism involved. The studies have reported that transcranial magnetic stimulation (TMS) may improve motor and other symptoms associated with neurodegenerative and neuropsychiatric processes such as major depression, schizophrenia, epilepsy, neuropathic pain, amyotrophic lateral sclerosis, progressive muscle atrophy, multiple sclerosis, stroke, Alzheimer's disease, Parkinson's disease or HD. This study focuses on the effect of TMS on oxidative stress and neurogenesis in studies and its possible usefulness in HD.

Olfactory bulbectomy induced oxidative and cell damage in rat: protective effect of melatonin.

In this study we analyzed the effects of melatonin (Mel, 1 mg/kg ip) on behavioral changes as well as cell and oxidative damage prompted by bilaterally olfactory bulbectomy. Olfactory bulbectomy caused an increase in lipid peroxidation products and caspase-3, whereas it prompted a decrease of reduced glutathione (GSH) content and antioxidative enzymes activities. Additionally, olfactory bulbectomy induced behavioral changes characterized by the enhancement of immobility time in the forced swim test and hyperactivity in the open field test. All these changes were normalized by treatment of Mel (14 days). Our data show that Mel has a beneficial neuropsychiatric action against oxidative stress, cell damage and behavior alterations.

[The molecular bases of Huntington's disease: the role played by oxidative stress]. / Bases moleculares de la enfermedad de Huntington: papel del estrés oxidativo.

INTRODUCTION: Huntington's disease is a neurodegenerative, autosomal dominant disease that mainly affects the basal ganglia. The disorder is caused by mutation in the gene encoding the huntingtin protein (Htt), producing intracellular aggregates. The adult form (chorea with dementia) is the most frequent. It is characterized by unpredictable, spasmodic, involuntary and constant movements, mostly associated with psychiatric and cognitive alterations. DEVELOPMENT: The main characteristics of Huntington's disease are: neuronal loss, glyosis, and accumulations of mutated Htt, all associated with different underlying channels in the pathogenesis of the disease, such as: excitotoxicity, energy deficit (ATP depletion), reduction in the synthesis and release of neurotrophic factors (BDNF and GDNF), and oxidative stress. Oxidative stress is involved in the pathogenesis of various neurodegenerative diseases, including Huntington's disease, and numerous studies have shown the existence of oxidative damage in the plasma and tissue of patients suffering from this disease. CONCLUSIONS: Oxidative stress in patients with Huntington's disease may be used as an evolutionary-prognostic marker of both the disease and therapeutic effectiveness, as well as an interesting field of research for the development of new therapeutic strategies.

Effect of melatonin on myocardial oxidative stress induced by experimental obstructive jaundice.

OBJECTIVE: melatonin has been demonstrated to have active antioxidant properties in different tissues during experimental cholestasis. The aim of this research was to study myocardial oxidative stress on obstructive jaundice, and to analyze the effect of melatonin on myocardial oxidative lesions. MATERIAL AND METHODS: we achieved cholestasis by ligature and sectioning of the main bile duct. Melatonin was administered intraperitoneally (500 microg/kg/day). We measured malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxydase (GPx) antioxidant enzyme levels in the heart tissue. RESULTS: obstructive cholestasis increased MDA and decreased GSH as well as all antioxidant enzymes. Melatonin administration significantly decreased MDA values, and increased GSH and antioxidant enzymes on the icteric animal myocardium. CONCLUSIONS: melatonin treatment prevents oxidative stress in the cardiac tissue as induced by experimental cholestasis.

[Model of Huntington's disease induced with 3-nitropropionic acid]. / Modelo de enfermedad de Huntington inducido con ácido 3-nitropropiónico.

INTRODUCTION: Huntington's disease is an autosomal dominant hereditary disorder. This neurodegenerative illness is characterized by mutation of the huntingtin protein gene, causing the formation of intracellular protein aggregates. DEVELOPMENT: Intensive research efforts have been made to investigate the molecular mechanism involved. For this reason, the development of animal and cellular models of Huntington's disease has offered alternative approaches to study of this disease. The alteration of succinate dehydrogenase activity has been linked to Huntington's disease. 3-nitropropionic acid is an inhibitor of this enzyme, prompting oxidative stress and death neuronal, mimic some aspects of Huntington's disease as anatomical, physiological and chemical changes. CONCLUSION: This model is a useful tool to study the mechanisms involved in this disease and to evaluate new therapeutic strategies.

[Changes in oxidative stress biomarkers induced by puberty]. / Cambios en biomarcadores del estrés oxidativo inducidos por la pubertad.

AIM: Evaluate the influence of puberty in oxidative stress. SUBJECTS AND METHODS: The study included 38 prepubescent males with Tanner G(1)-P(1) and 32 healthy pubescent boys with Tanner G(3-4)-P(3-4). Weight, height and body mass index, heart rate, blood pressure values were within the 50 percentile 50+/-1SD for their age. The biomarkers were measured in saliva, as a good correlation between saliva and plasma levels has been reported in lipoperoxidation products, reduced glutathione and catalase. RESULTS: Pubescent boys had significantly higher levels of lipoperoxidation products (P<0.001) compared with the prepubertal group, with no significant differences in the other parameters measured. There was a significant positive correlation between lipoperoxides and reduced glutathione in these children. CONCLUSION: It is the first time that an increase of lipoperoxidation products has been reported in pubertal boys and this biomarker could play a role in the development of oxidative stress in this stage of life.

Effects of magnetic stimulation on oxidative stress and skeletal muscle regeneration induced by mepivacaine in rat.

We investigated the effect of magnetic field stimulation (MS) on oxidative damage and skeletal muscle injury prompted by mepivacaine injection in the anterior tibial muscle of Wistar rats. The effects of mepivacaine and MS on oxidative stress were evaluated by lipid peroxidation, GSH levels and catalase activity. Muscle regeneration was analyzed by haematoxylin-eosin stained, NADH-TR histochemical reaction, desmin immunostaining as well as by morphometric parameters such as fibers density and fiber area were evaluated. Our data revealed that mepivacaine induced oxidative stress, that MS prevents the harmful effects induced by mepivacaine and that it facilitates the regeneration process of skeletal muscle. In conclusion, the results show the ability of MS to modify skeletal muscle response to mepivacaine.

Neuroprotective effect of carvedilol and melatonin on 3-nitropropionic acid-induced neurotoxicity in neuroblastoma.

In neurodegenerative diseases, progressive oxidative stress is a major event that precedes neuronal death. Oxidative stress is characterized by an imbalance between oxidants and antioxidants. This imbalance induced oxidative molecular and cell damage, reducing cellular viability. 3-Nitropropionic acid (3NP) causes oxidative stress and other molecular and cellular changes similar to those observed in neurons of patients with Huntington's disease. Since carvedilol and melatonin act as free-radical scavengers, this study examined the effect of carvedilol (10(-5) M) and melatonin (10(-5) M) on oxidative and cell damage induced by 3NP in N1E-115 neuroblastoma cells. Carvedilol and melatonin prevented the increases in lipid peroxidation and total LDH activity, as well as the depletion of reduced glutathione (GSH) and the reduction of antioxidative enzymes activities in N1E-115 cells incubated with 100 mM 3NP. All these carvedilol and melatonin effects were more intense when the drugs were added before rather than after inducing the damage by 3NP. These results also provided evidence supporting the hypothesis that carvedilol and melatonin can be useful for treating neurodegenerative diseases, such as Huntington's disease.

Fat overload aggravates oxidative stress in patients with the metabolic syndrome.

BACKGROUND: Patients with the metabolic syndrome have greater levels of oxidative stress. However, as the response of markers of this stress to a fat overload is unknown, we evaluated certain markers of oxidative stress in these patients. MATERIAL AND METHODS: The study population comprised 93 subjects (70 men and 23 women): 13 healthy people (controls) with a mean age of 48.81 +/- 9.01 years and 80 patients with the metabolic syndrome (mean age, 43.25 +/- 11.55 years), according to the Adult Treatment Panel III criteria. All the participants were given a 60 g fat overload (Supracal). Three hours later the following biomarkers of oxidative stress were measured: lipid peroxidation products, protein carbonyl groups, reduced glutathione, glutathione peroxidase (GSH-Px), catalase, superoxide dismutase, glutathione reductase (GSH-Road) and glutathione S-transferase. The levels of oxidized glutathione (GSSG) were calculated. RESULTS: Compared with the controls, the patients showed greater baseline oxidative stress, higher levels of lipid peroxidation products and oxidized glutathione, and lower levels of reduced glutathione, glutathione peroxidase activity, glutathione reductase and glutathione transferase. This stress was more intense after the subjects received a fat overload, more so in the patients who experienced a greater reduction in GSHpx and GSHrd antioxidant activity and a greater increase in the levels of carbonylated proteins and lipoperoxides than the controls. CONCLUSIONS: Patients with the metabolic syndrome have greater oxidative stress than healthy people. The variation in markers of this stress after a fat overload was even more pronounced in the patients.