Acute exercise increases plasma total antioxidant status and antioxidant enzyme activities in untrained men.

Antioxidant defences are essential for cellular redox regulation. Since free-radical production may be enhanced by physical activity, herein, we evaluated the effect of acute exercise on total antioxidant status (TAS) and the plasma activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase and its possible relation to oxidative stress resulting from exercise. Healthy untrained male subjects (n = 34) performed three cycloergometric tests, including maximal and submaximal episodes. Venous blood samples were collected before and immediately after each different exercise. TAS and enzyme activities were assessed by spectrophotometry. An increase of the antioxidant enzyme activities in plasma was detected after both maximal and submaximal exercise periods. Moreover, under our experimental conditions, exercise also led to an augmentation of TAS levels. These findings are consistent with the idea that acute exercise may play a beneficial role because of its ability to increase antioxidant defense mechanisms through a redox sensitive pathway.

Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans.

Optimal levels of membrane fluidity are essential for numerous cell functions including cell growth, solute transport and signal transduction. Since exercise enhances free radical production, our aim was to evaluate in healthy male subjects the effects of an acute bout of maximal and submaximal exercise on the erythrocyte membrane fluidity and its possible relation to the oxidative damage overproduction due to exercise. Subjects (n = 34) performed three cycloergometric tests: a continuous progressive exercise, a strenuous exercise until exhaustion and an acute bout of exercise at an intensity corresponding to 70% of maximal work capacity for 30 min. Venous blood samples were collected before and immediately after these exercises. Erythrocyte membrane fluidity was assessed by fluorescence spectroscopy. Plasma malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl content of plasmatic proteins were used as an index of lipid and protein oxidation, respectively. Exercise produced a dramatic drop in the erythrocyte membrane fluidity as compared to resting time, but this was not accompanied by significant changes in the plasmatic MDA and 4-HDA concentrations. The highest erythrocyte membrane rigidity was detected immediately after strenuous exercise until exhaustion was performed. Protein carbonyl levels were higher after exhaustive exercises than at rest. Continuous progressive and strenuous exercises until exhaustion, but not submaximal workload, resulted in a significant enhanced accumulation of carbonylated proteins in the plasma. These findings are consistent with the idea that exercise exaggerates oxidative damage, which may contribute, at least partially, to explain the rigidity in the membrane of the erythrocytes due to acute exercise.

Melatonin reduces membrane rigidity and oxidative damage in the brain of SAMP8 mice.

We evaluated the autophagy-lysosomal pathway and membrane fluidity in brain cells and mitochondrial membranes obtained from senescence-accelerated (SAMP(8)) and senescence-resistant (SAMR(1)) mice at 5 and 10 months of age. Moreover, we studied whether chronic treatment from age 1 to 10 months with melatonin stabilizes membrane fluidity. Fluidity was measured by polarization changes of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene-p-toluene sulfonate. Results showed that in untreated animals at 5 months of age, synaptosomal and mitochondrial fluidity was decreased in SAMP(8) compared to SAMR(1), as was the cathepsin D/B ratio, indicating dysfunction of the autophagy-lysosomal pathway. Moreover, we detected synaptosomal rigidity and programmed cell death capability in both groups at 10 months of age. Mitochondrial fluidity, however, did not show a significant age-dependent change but was lower in SAMP(8) than in SAMR(1) at the 5- and 10-month time points. Melatonin administration prevented rigidity in the mitochondrial membrane and seemed to decrease age-related autophagy-lysosomal alterations. These data suggest that melatonin may act to slow down the aging process because of its ability to enhance membrane fluidity and maintain structural pathways.

In vivo hepatic oxidative stress because of carbon tetrachloride toxicity: protection by melatonin and pinoline.

The protective in vivo effects of melatonin or pinoline on carbon tetrachloride (CCl(4))-induced oxidative damage were investigated in liver of rats and compared to rats injected only with CCl(4) (5 mL/kg body weight). Hepatic cell membrane fluidity, monitored using fluorescence spectroscopy, exhibited a significant decrease in animals exposed to CCl(4) compared to control rats. Increases in lipid and protein oxidation, as assessed by concentrations of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA), and protein carbonylation, respectively, were also seen in hepatic homogenates of animals exposed to CCl(4). The administration of melatonin (10 mg/kg body weight) or pinoline injected 30 min before and 1 hr after CCl(4), fully prevented membrane rigidity and protein oxidation. However, treatment with melatonin was more effective in terms of reducing lipid peroxidation than pinoline, as the increases in MDA+4-HDA levels because of CCl(4) were reduced by 93.4% and 34.4% for melatonin or pinoline, respectively. Livers from CCl(4)-injected rats showed several histopathological alterations; above all, there were signs of necrosis and ballooning degeneration. The concurrent administration of melatonin or pinoline reduced the severity of these morphological changes. On the basis of the biochemical and histopathological findings, we conclude that both melatonin and pinoline were highly effective in protecting the liver against oxidative damage and membrane rigidity because of CCl(4). Therefore, these indoles may be useful as cotreatments for patients with hepatic intoxication induced by CCl(4).

Efecto protector de 5-metoxi-indolaminas pineales en la oxidación de sinaptosomas mediada por radicales libres / No disponible

No disponible

Estudio de la repercusión del estrés oxidativo sobre la fluidez de membrana en un modelo animal de la esclerosis lateral amiotrófica / No disponible

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Peorxidación lipídica en pacientes afectos de tumores del sistema nervioso central / No disponible

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Efecto protector de la melatonina frente a la toxicidad de la mitomicina C / No disponible

No disponible

Effects of tryptophan and 5-hydroxytryptophan on the hepatic cell membrane rigidity due to oxidative stress.

The ability of several indoleamines to scavenge free radicals is well documented. Our aim was to evaluate the ability of 0.01-3 mM tryptophan (Trp) and 0.1-5 mM 5-hydroxytryptophan (5-OH-Trp) to protect hepatic cell membranes against 0.1 mM FeCl(3) plus 0.1 mM ascorbic acid-induced lipid peroxidation and increases in membrane rigidity. Membrane fluidity was evaluated using fluorescence spectroscopy. Lipid and protein oxidation were estimated by quantifying malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HDA) concentrations and carbonyl group content, respectively. Exposure to FeCl(3) plus ascorbic acid increased hepatic cell membrane rigidity, MDA + 4-HDA and carbonyl content. The presence of 5-OH-Trp, but not Trp, attenuated these changes. In the absence of oxidative stress, neither indoleamine modified fluidity, MDA + 4-HDA or carbonylation. These results suggest that C5 hydroxylation determines the ability of Trp to preserve membrane fluidity in the presence of oxidative stress.

Protective effect of melatonin against mitomycin C-induced genotoxic damage in peripheral blood of rats.

Mitomycin C (MMC) generates free radicals when metabolized. We investigated the effect of melatonin against MMC-induced genotoxicity in polychromatic erythrocytes and MMC-induced lipid peroxidation in brain and liver homogenates. Rats (N = 36) were classified into 4 groups: control, melatonin, MMC, and MMC + melatonin. Melatonin and MMC doses of 10 mg/kg and 2 mg/kg, respectively, were injected intraperitoneally. Peripheral blood samples were collected at 0, 24, 48, 72, and 96 hours posttreatment and homogenates were obtained at 96 hours posttreatment. The number of micronucleated polychromatic erythrocytes (MN-PCE) per 1000 PCE was used as a genotoxic marker. Malondialdehyde (MDA) plus 4-hydroxyalkenal (4-HDA) levels were used as an index of lipid peroxidation. The MMC group showed a significant increase in MN-PCE at 24, 48, 72, and 96 hours that was significantly reduced with melatonin begin coadministrated. No significant differences were found in lipid peroxidation. Our results indicate that MMC-induced genotoxicity can be reduced by melatonin.

Protective effect of melatonin and pinoline on nitric oxide-induced lipid and protein peroxidation in rat brain homogenates.

Nitric oxide (NO) is a physiological neurotransmitter, a mediator of the excitatory neurotransmitter glutamate pathways that regulates several neuroendocrine functions, but excessive NO is toxic by itself and it interacts with superoxide radical (O(2)(-)) to form the peroxynitrite anion (ONOO(-)). Using rat brain homogenates, we investigated the effects of melatonin and pinoline in preventing the level of lipid peroxidation (LPO) and carbonyl contents in proteins induced by nitric oxide (NO) which was released by the addition of sodium nitroprusside (SNP). Lipid and protein peroxidation were estimated by quantifying malondialdehyde (MDA) and 4-hydroxyalkenal (4-HDA) concentrations and carbonyl contents, respectively. SNP increased MDA+4-HDA and carbonyl contents production in brain homogenates in a time and concentration dependent manner. Both, melatonin and pinoline reduced NO-induced LPO and carbonyl contents in a dose-dependent manner in concentrations from 0.03 to 3 mM and 1 to 300 microM, respectively. Under the in vitro conditions of this experiment, both antioxidants were more efficient in limiting SNP protein oxidation than lipid damage.

Effects of trace elements on membrane fluidity.

According to the Fluid Mosaic Model, a biological membrane is a two-dimensional fluid of oriented proteins and lipids. The lipid bilayer is the basic structure of all cell and organelle membranes. Cell membranes are dynamic, fluid structures, and most of their molecules are able to move in the plane of the membrane. Fluidity is the quality of ease of movement and represents the reciprocal value of membrane viscosity. Fluid properties of biological membranes are essential for numerous cell functions. Even slight changes in membrane fluidity may cause aberrant function and pathological processes. Several evidences suggest that trace elements, e.g., iron, copper, zinc, selenium, chromium, cadmium, mercury and lead may influence membrane fluidity. The interaction of heavy metals with cellular membranes may contribute to explain, at least partially, the toxicity associated with these metals.

Melatonin improves deferoxamine antioxidant activity in protecting against lipid peroxidation caused by hydrogen peroxide in rat brain homogenates.

Deferoxamine (DF) is an antioxidant molecule because of its ability to chelate iron. This study compared the ability of DF alone or in combination with melatonin, 5-methoxytryptophol or pinoline in preventing lipid peroxidation due to hydrogen peroxide (H(2)O(2)) in rat brain homogenates. Malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) in the homogenates were measured as indices of lipid peroxidation. Incubation of homogenates with DF reduced, in a dose-dependent manner, MDA+4-HDA formation due to H(2)O(2). When melatonin, 5-methoxytryptophol or pinoline were added to the incubation medium, the efficacy of DF in preventing lipid peroxidation was enhanced. These cooperative effects between DF, melatonin, and related pineal products may be important in protecting tissues from the oxidative stress due to iron overload.

N-acetylserotonin suppresses hepatic microsomal membrane rigidity associated with lipid peroxidation.

N-acetylserotonin, the immediate precursor of melatonin in the tryptophan metabolic pathway in the pineal gland, has been reported to be an antioxidant. The aim of this work was to test the effect of N-acetylserotonin in stabilizing biological membranes against oxidative stress. Hepatic microsomal membranes from male adult rats were incubated with N-acetylserotonin (0.001-3 mM) before inducing lipid peroxidation using FeCl(3), ADP and NADPH. Control experiments were done by incubating microsomal membranes with N-acetylserotonin in the absence of lipid peroxidation-inducing drugs. Membrane fluidity was assessed by fluorescence spectroscopy and malonaldehyde plus 4-hydroxyalkenals concentrations were measured to estimate the degree of lipid peroxidation. Free radicals induced by the combination of FeCl(3)+ADP+NADPH produced a significant decrease in the microsomal membrane fluidity, which was associated with an increase in the malonaldehyde plus 4-hydroxyalkenals levels. These changes were suppressed in a concentration-dependent manner when N-acetylserotonin was added in the incubation buffer. In the absence of lipid peroxidation, N-acetylserotonin (0.001-3 mM) did not change membrane fluidity nor malonaldehyde plus 4-hydroxyalkenals levels. These results suggest that the protective role of N-acetylserotonin in preserving optimal levels of fluidity of the biological membranes may be related to its ability to reduce lipid peroxidation.

Protective effect of beta-carbolines and other antioxidants on lipid peroxidation due to hydrogen peroxide in rat brain homogenates.

Tryptoline and pinoline are two beta-carbolines isolated from the nervous system of mammals. We investigated the ability of these compounds to prevent lipid peroxidation induced by hydrogen peroxide in rat brain homogenates. We also compared their effects with other known antioxidants including melatonin, trolox and ascorbic acid. Lipid peroxidation was assessed by measuring malonaldehyde (MDA) and 4-hydroxy-alkenals (4-HDA) concentrations in the brain homogenates. Incubation with hydrogen peroxide (5 mM) increased MDA+4-HDA levels, which were totally prevented by tryptoline, pinoline, melatonin and trolox in a concentration-dependent manner. By contrast, higher MDA-4-HDA concentrations compared with control experiments were found after incubation with ascorbic acid, thus reflecting an increase of lipid peroxidation induced by this compound. Although in vivo studies are needed, the data suggest that these beta-carbolines may be potential neuroprotective agents because of their antioxidant activities.

Ferrum metabolism after permanence at extreme altitude on Mount Everest.

High altitude has always intrigued physiologists because of the remarkable ability of man to adapt to the hostile environment. Despite numerous studies examining the physiological alterations occurring during exercise after exposure to hypoxia and the adaptative effects of sustained residence at altitude, several issues remain unresolved. The aim of investigation of the Spanish Medical Research Expedition to Mount Everest in 1992 was an extensive study on the physiological adaptations to the hypobaric environment at extreme altitude. We are presenting advance results the gasometry, acid-base parameters and ferrum metabolism.

[Hematic parameters in chronic hypoxemia]. / Parámetros hemáticos en hipoxemia crónica.

The hematic effects of hypoxia have been studied in 184 patients divided in four groups: 1) 10 patients with pO2 values in capillary blood lower than 43 mmHg; 2) 40 patients with pO2 between 43 and 50 mmHg; 3) 134 subjects with pO2 between 51 and 62 mmHg; and 4) 39 normal subjects (control). Hypoxemic subjects show higher erythrocyte concentrations than normoxemic ones, but without reaching the point of polycythemia and without significant differences in the hemoglobin concentration. The values of the mean corpuscular volume, the mean corpuscular hemoglobin and the concentration of the mean corpuscular hemoglobin show no significant differences between the groups. The amplitude of the red corpuscle distribution has not shown statistically significant differences between the groups of more pronounced hypoxia and those of slight hypoxia and control. The hematocrit, determined in the autoanalyzer, does not show any significant differences between the groups, whereas the one obtained by centrifugation is higher in the hypoxemic groups. Differences are non-significant in platelet count, mean platelet volume, and platelet distribution among the groups. The leucocyte count yields progressively higher values as blood pO2 decreases, with an accompanying increase in the percentage of neutrophyle granulocytes and a decrease in lymphocytes. Leucocytes with peroxidasic activity are significantly higher when the oxygen offer is lower.

[Effects of hypoxia on plasma concentrations and daily elimination of sodium, potassium and chlorine ions]. / Efectos de la hipoxia sobre las concentraciones séricas y la eliminación diaria de los iones sodio, potasio y cloruro.

Serum concentrations of Na+, K+ and Cl- are studied, as well as the elimination of these ions in urine, in patients suffering from chronic respiratory insufficiency, being classified in two groups according to the level of hypoxemia: group A (PO2 less than 6.66 KPa) and group B (PO2 less than 8 KPa). A third group C of healthy patients with analogous anthropological characteristics has served as a control group. The concentrations of serum of the three ions are noticeably similar in the three groups, but the daily elimination of Na+, K+ and Cl- is less in those suffering from respiratory insufficiency than in those of the control group, with significant statistical differences in all cases except with K+ in those suffering from pronounced hypoxemia. On analysing the correlation between the rates of elimination of ions in urine, with the plasmatic values of PO2, PCO2 and [H+] of all the patients studied, the highest values of the Pearson coefficient are found on correlating the elimination of ions with the partial pressures of oxygen, therefore suggesting that hypoxia could be the main motor inducing metabolic changes.

Effects of chronic hypoxia on kidney function.

Renal disfunctions which appear in the chronic respiratory insufficient patient are analysed, as well as the participation of the arterial blood hypoxemia in their genesis. Renal clearances of Na, K, Cl, Ca, Mg and Pi, and those of urea and creatinine, were lower in 36 patients having chronic hypoxemia than in 15 normosemic controls, showing significant statistical differences for Na, K, Cl, Ca and urea. The correlations between the clearances of these substances and the pO2 arterial blood levels had a greater statistical significance than can be established with pCO2 or [H+] levels. Thus, the existence of a causal dependency between renal disfunction and hypoxemia may be deduced.