Inés Sánchez-Sellero

Antioxidant properties of dimethyl sulfoxide and its viability as a solvent in the evaluation of neuroprotective antioxidants

INTRODUCTION Dimethyl sulfoxide is an amphiphilic compound whose miscibility with water and its ability to dissolve lipophilic compounds make it an appreciated solvent in biomedical research. However, its reported antioxidant properties raise doubts about its use as a solvent in evaluating new antioxidants. The goal of this investigation was to evaluate its antioxidant properties and carry out a comparative study on the antioxidant properties of some known neuroprotective antioxidants in the presence and absence of dimethyl sulfoxide. METHODS The antioxidant properties of dimethyl sulfoxide were studied in rat brain homogenates by determining its ability to reduce both lipid peroxidation (TBARS formation) and protein oxidation (increase in protein carbonyl content and decrease in free thiol content) induced by ferrous chloride/hydrogen peroxide. Its ability to reduce the production of hydroxyl radicals by 6-hydroxydopamine autoxidation was also estimated. The same study was also performed with three known antioxidants (α-phenyl-N-tert-butylnitrone; 2-methyl-2-nitrosopropane; 5,5-dimethyl-1-pyrroline N-oxide) in the presence and absence of dimethyl sulfoxide. RESULTS Our results showed that dimethyl sulfoxide is able to reduce both lipid peroxidation and protein carbonyl formation induced by ferrous chloride/hydrogen peroxide in rat brain homogenates. It can also reduce the production of hydroxyl radicals during 6-hydroxydopamine autoxidation. However, it increases the oxidation of protein thiol groups caused by ferrous chloride/hydrogen peroxide in rat brain homogenate. DISCUSSION Despite the here reported antioxidant and pro-oxidant properties of dimethyl sulfoxide, the results obtained with α-phenyl-N-tert-butylnitrone, 2-methyl-2-nitrosopropane, and 5,5-dimethyl-1-pyrroline N-oxide corroborate the antioxidant properties attributed to these compounds and support the potential use of dimethyl sulfoxide as a solvent in the study of the antioxidant properties of lipophilic compounds. CONCLUSION Dimethyl sulfoxide is a very useful solvent that may be used at relatively low concentrations in the development of new antioxidants with neuroprotective properties.

Brain oxidative stress and selective behaviour of aluminium in specific areas of rat brain: potential effects in a 6-OHDA-induced model of Parkinson’s disease

J. Neurochem. (2009) 109, 879–888.

Inhibition of brain monoamine oxidase activity by the generation of hydroxyl radicals: potential implications in relation to oxidative stress.

Monoamine oxidase (MAO) is an enzyme involved in brain catabolism of monoamine neurotransmitters whose oxidative deamination results in the production of hydrogen peroxide. It has been documented that hydrogen peroxide derived from MAO activity represents a special source of oxidative stress in the brain. In this study we investigated the potential effects of the production of hydroxyl radicals (*OH) on MAO-A and MAO-B activities using mitochondrial preparations obtained from rat brain. Ascorbic acid (100 microM) and Fe2+ (0.2, 0.4, 0.8, and 1.6 microM) were used to induce the production of *OH. Results showed that the generation of *OH significantly reduced both MAO-A (85-53%) and MAO-B (77-39%) activities, exhibiting a linear correlation between both MAO-A and MAO-B activities and the amount of *OH produced. The reported inhibition was found to be irreversible for both MAO-A and MAO-B. Assuming the proven contribution of MAO activity to brain oxidative stress, this inhibition appears to reduce this contribution when an overproduction of *OH occurs.

In vitro inhibition of catalase activity by cigarette smoke: relevance for oxidative stress

The in vitro effects of cigarette smoke on catalase activity were investigated in biological preparations from rat liver and brain using a polarographic method. In both cases cigarette smoke solutions showed a potent ability to inhibit catalase activity with a slight time dependency. The reversibility of their inhibitory activity was demonstrated by in vitro dialysis tests. The catalase inhibitory compound(s) are formed in the smoking process, are not extracted with organic solvents and appear to have a relatively low molecular weight. We also examined the effects obtained by using two different commercial blends of tobacco, achieving a major inhibition with Burley tobacco in comparison to Bright tobacco. These data suggest that the cytotoxic and mutagenic effects of cigarette smoke may be mediated by its additional capacity to enhance the generation of free radicals by inhibiting catalase activity, thus contributing to cell damage particularly during oxidative stress.Copyright

Reduction of rat brain levels of the endogenous dopaminergic proneurotoxins 1,2,3,4-tetrahydroisoquinoline and 1,2,3,4-tetrahydro-β-carboline by cigarette smoke

1,2,3,4-Tetrahydroisoquinoline (TIQ) and 1,2,3,4-tetrahydro-beta-carboline (THbetaC) are two endogenous or exogenous dopaminergic proneurotoxicants supposedly involved in the etiology of Parkinsons disease. We investigated whether the chronic administration of a twice daily dose of a cigarette smoke solution might modify the endogenous concentrations of TIQ and THbetaC in rat brain. Using gas chromatography/mass spectrometry (GC-MS) we found a significant reduction in the brain levels of both proneurotoxins after 30 days of treatment. The reduction in the brain levels of both compounds was more significant using Burley rather than Bright tobacco. These results suggest that cigarette smoke may prevent the accumulation of these proneurotoxins in the brain, which corroborate the involvement of the reaction between both TIQ and THbetaC with some components of tobacco smoke as a neuroprotective mechanism for Parkinsons disease.

Studies on the interaction between 1,2,3,4-tetrahydro-β-carboline and cigarette smoke: a potential mechanism of neuroprotection for Parkinson's disease

Abstract 1,2,3,4-Tetrahydro-β-carboline (THβC) is an endogenous or environmental neurotoxic factor putatively involved in the development of Parkinsons disease (PD). As part of our efforts to characterize the mechanism of the reported protection of smoking against PD, we have examined the interaction between THβC and cigarette smoke. We found that THβC reacts in vitro and under physiological conditions with some components of cigarette smoke to form N 2 -(cyanomethyl)-THβC (CM-THβC), N 2 -(1′-cyanoethyl)-THβC (CE-THβC), N 2 -(1′-cyanopropyl)-THβC (CP-THβC), N 2 -(1′-cyanobutyl)-THβC (CB-THβC) and N 2 -formyl-THβC (F-THβC). Significant differences in the recovery of some of these THβC-derivatives were obtained for Burley and Bright tobacco. Several of the reported compounds showed reversible and competitive MAO-A inhibitory properties. The detection of some of these compounds in rat brain after chronic administration of THβC and a solution of cigarette smoke proved that the reported interactions also occur in vivo. These results are discussed as a potential mechanism of neuroprotection in the development of PD.

Caffeine intake and Menière's disease: Is there relationship?

Objectives: Although it is commonly recognized that dietary restrictions may improve the clinical course of Menières disease, their effectiveness has not been definitely demonstrated. The aim of this study was to examine whether caffeine consumption could be involved in Menières disease. Methods: Cross-sectional, observational, case-control study, comparing caffeine consumption (intake of coffee, tea, kola-type beverages, energy drinks, and chocolate-containing beverages or foods) between patients with Menières disease (group A) and patients affected by vertigo with other origins (group B) and/or control subjects (group C). Patients: 180 subjects (72 in group A, 72 in group B, and 36 in group C). Caffeine intake was categorized in four levels: very low (0–25 mg/day), low (26–100 mg/day), moderate (101–300 mg/day), and high (≥301 mg/day). Very low and low intake were considered light consumption, and moderate and high intake, heavy consumption. Results: Mean daily caffeine intake was 175.8 mg. Menières disease patients showed a daily caffeine intake (222 mg) greater than those not affected by this disease (145 mg). Excluding in group B migraine patients, differences in caffeine intake are significant among the three groups (P = 0.021). There were significantly more heavy-consumers in group A than in other two groups jointed (P = 0.024; OR = 1.301, IC95% (1.015;1.668)). In group A, the age at onset of symptoms in caffeine consumers (49.7 years) was lower than in non-consumers (55.9 years). Discussion: It should be recommended to reduce caffeine intake in those population groups with higher risk of Menières disease (e.g. subjects with family members suffering from this disease). GRAPHICAL ABSTRACT

Alcohol consumption in Menière’s disease patients

Objectives: Dietary changes are useful in the management of Menière’s disease; regarding alcohol, many clinicians recommend to avoid or reduce its consumption. However, there are no researches aimed to evaluate whether habitual alcohol consumption is more prevalent and/or more intense in patients with Menière’s disease. Methods: Cross-sectional, observational, case-control study, including three groups: patients with Menière’s disease, patients with vertigo of other origins, and control subjects. Alcohol consumption was compared between these three groups. Participants in this study were grouped according to alcohol consumption as follows: categorization A1 (nonalcohol vs. alcohol consumers), categorization A2 (nonalcohol, low, moderate, and high alcohol consumers), and categorization A3 (light alcohol consumers: nonconsumers plus low consumers; heavy alcohol consumers: moderate plus high consumers). Results: A total of 180 subjects were included in this study (72 in group A, 72 in group B, and 36 in control group); 117 were women. The mean age was 52.7 years. Mean alcohol consumption was 41.22 g/week. Average consumption of alcohol in group A (50.42 g/week) was higher than in other two groups (36.53 g/week in B and 32.22 g/week in C), but differences were not statistically significant. In Menière’s group, light alcohol consumers showed age at onset of symptoms (49.39 years) lower than heavy alcohol consumers (55.51 years). No relationship was observed between alcohol consumption and uni or bilateral affectation. Discussion: It is possible that alcohol consumption delays the age at onset of Menière’s disease. A hypothetical explanation is the inhibitory effect of alcohol on hypothalamic production of vasopressin. A reduced release of this neurohormone would increase diuresis and decrease endolymphatic pressure. GRAPHICAL ABSTRACT