Biomedical subjects

M López-Torres

Publications and source records attributed to M López-Torres.

36 records · Page 2Linked to original sources

PubMed1993

Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs.

Brain catalase was continuously depleted throughout the life span starting with a large population of initially young and old frogs. Free radical-related parameters were measured in the brain tissue once per year after 2.5, 14.5, and 26.5 months of experimentation. Brain lipofuscin accumulation was observed after 14.5 and 26.5 months, and survival was continuously followed during 33 months. The age of the animal did not decrease endogenous antioxidants nor increase tissue peroxidation either in cross-sectional or longitudinal comparisons. Continuous catalase depletion similarly affected young and old animals, inducing glutathione reductase, tending to decrease oxidized glutathione/reduced glutathione (GSSG/GSH) ratio, decreasing lipofuscin accumulation in the brain, and increasing survival from 46% to 91% after 14.5 months. At 26.5 months of experimentation the loss of the glutathione reductase induction in catalase-depleted animals was accompanied by the presence of higher lipofuscin deposits than in controls and was followed by a great increase in mortality rate. Even though the maximal life span (7 years) was the same in the control and treated animals which were already old (4.2 years) at the beginning of the experiment, the treated animals showed a strong reduction in the rates of early death. It is proposed that the maintenance of a high antioxidant/prooxidant balance in the vertebrate brain greatly increases the probability of the individual to reach the final segments of its species-specific life span.

Aging↗

PubMed1993

Relationship between lipid peroxidation, fatty acid composition, and ascorbic acid in the liver during carbohydrate and caloric restriction in mice.

Growing OF1 mice were treated on a short-term basis with ad libitum, caloric-restricted, or carbohydrate-restricted diets, maintaining the same intake of vitamins and minerals in the three groups. Caloric intake was 60% of controls both in the caloric-restricted and in the carbohydrate-restricted groups. Neither global nor carbohydrate restriction changed liver superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, cytochrome oxidase, GSH, uric acid, or malondialdehyde (HPLC). Ascorbate was decreased in both restricted groups. Carbohydrate restriction, but not caloric restriction, increased unsaturation indexes of fatty acids in all lipid classes analyzed and increased sensitivity to peroxidation by one order of magnitude. It is concluded that short-term caloric restriction does not seem to increase antioxidants and decrease peroxidation in the mouse liver whereas long-term restriction can avoid decreases of antioxidants and increases of peroxidation during aging. Our experiments support the prevailing view that the caloric restriction phenomenon is due to a reduction in calories themselves instead of to a reduction in carbohydrates. This last manipulation strongly increases sensitivity to peroxidative damage in the liver. The results show that in vivo fatty acid unsaturation is a main factor in determining the sensitivity to lipid peroxidation.

Animals↗

PubMed1993

Simultaneous induction of sod, glutathione reductase, GSH, and ascorbate in liver and kidney correlates with survival during aging.

Catalase was continuously inhibited with aminotriazole in the liver and kidney during 33 months in large populations of old and young frogs in order to study the effects of the modification of the tissue antioxidant/prooxidant balance on the life span of a vertebrate species showing an oxygen consumption rate similar to that of humans. Free-radical-related parameters were measured during three consecutive years at 2.5, 14.5, and 26.5 months of experimentation. Aging per se did not decrease antioxidant enzymes and did not increase peroxidation (thiobarbituric acid positive substances, or high-pressure liquid chromatography [HPLC]-malondialdehyde), either cross sectionally or longitudinally. Long-term catalase inhibition leads to time-dependent increases (100-900%) of endogenous superoxide dismutase, GSH, ascorbate, and especially glutathione reductase at 2.5 and 14.5 months of experimentation. This was positively correlated with a higher survival of treated animals (91% in treated versus 46% in controls at 14.5 months of experimentation). The loss of those inductions after 26.5 months leads to a sharp increase in mortality rate. The results show for the first time that simultaneous induction of various tissue antioxidant enzymes and nonenzymatic antioxidants can increase the mean life span of a vertebrate animal. It is concluded that the tissue antioxidant/prooxidant balance is a strong determinant of mean life span.

Aging↗

PubMed1992

Relationship between antioxidants, lipid peroxidation and aging.

Experiments performed on species as different as flies, rats and frogs are not conclusive about the possibility that antioxidant defenses decrease in old animals. Even when these decreases are found, their physiological meaning is far from clear. Furthermore, a constancy of antioxidant capacity in old age is consistent with the fact that aging is a progressive phenomenon which occurs at a rather constant rate from the mature young to the very old animal, without showing a great acceleration rate in the aged. Nevertheless, experimental results strongly suggest that the maintenance of an appropriate antioxidant/prooxidant balance does have an important role in maintaining health in the aging animal. It is possible that the continuous presence of small amounts of free radicals in the adult tissues of both mature adults and old animals is an important factor in aging (a progressive phenomenon) and susceptibility to disease. Since, similarly to what occurs in procariota, the whole antioxidant system seems to be under homeostatic control in vertebrates, it is imperative to perform comprehensive and detailed studies on the effects of carefully controlled doses of antioxidants on biomarkers of health as well as on the different endogenous cellular antioxidant and prooxidant systems. These studies should have as a final goal the knowledge of which doses of antioxidants are high enough to increase antioxidant protection but low enough to avoid feedback depression of other endogenous antioxidants; this could further improve the health state of humans situated in the middle and last phases of their life span.

Aging↗

PubMed1992

Sensitivity to in vitro lipid peroxidation in liver and brain of aged rats.

Lipid peroxidation in rat liver and brain has been studied to see if it increases with old age. No significant differences in the level of endogenous, nonstimulated lipid peroxidation (TBA-RS) is found between 9 month-old (mature adults) and 28 month-old animals in liver or cerebral cortex. Liver homogenates subjected in vitro to an oxidative stress (ascorbate-Fe++), show a clearly slower peroxidation rate in old than in young animals. On the other hand, the in vitro peroxidation rate of cerebral homogenates was similar in young and old animals. The in vitro peroxidation rate was much higher in brain than in liver tissue. These results do not support the view that old rats liver and brain are more susceptible to free radical oxidative damage than those of young ones.

Aging↗

PubMed1991

Simultaneous determination of two antioxidants, uric and ascorbic acid, in animal tissue by high-performance liquid chromatography.

A rapid and simple method for the simultaneous analysis of uric and ascorbic acid in extracts of animal tissue is described. The method uses reversed-phase ion-pair chromatography with ultraviolet detection. The technique allows efficient separation of both acids while showing high selectivity, recovery, reproducibility, and sample stability. Calculated levels of both substances in mouse liver tissue were 1.00 +/- 0.05 mumol ascorbic acid/g and 130 +/- 5 nmol uric acid/g.

Animals↗

PubMed1991

Effect of cold acclimation on GSH, antioxidant enzymes and lipid peroxidation in brown adipose tissue.

Cold acclimation increased the activities of superoxide dismutase, catalase, total and selenium (Se)-dependent glutathione peroxidases (GPx) and glutathione reductase by 2-4-fold in the brown adipose tissue (BAT) of cold-acclimated rats. Nevertheless, when expressed per unit protein, the antioxidant enzyme activities were unaltered. Sensitivity to lipid peroxidation and GSH levels both increased by one order of magnitude in the cold on a per weight basis and were still 3-5 times greater in the cold when expressed per mg of protein. We suggest that activation of BAT leads to a large increase in the potential for lipid peroxidation and that the tissue responds to this challenge by increasing practically all of its antioxidant defences. Nevertheless, GSH, and possibly GPx activity, seem to be the principal defences involved in adaptation of the tissue to a higher sensitivity to peroxidative damage after activation.

Acclimatization↗

PubMed1991

Effect of natural ageing and antioxidant inhibition on liver antioxidant enzymes, glutathione system, peroxidation, and oxygen consumption in Rana perezi.

A study of the physiological role of oxygen free radicals in relation to the ageing process was performed using the liver of Rana perezi, an animal with a moderate rate of oxygen consumption and a life span substantially longer than that of laboratory rodents. Among the five different antioxidant enzymes only superoxide dismutase (SOD) showed an age-dependent decrease. Cytochrome oxidase (COX), glutathione status, in vivo and in vitro liver peroxidation, and metabolic rate did not vary as a function of age. Long-term (2.5 months) treatment with aminotriazole and diethyldithiocarbamate depleted catalase (CAT) activity and did not change both glutathione peroxidases (GPx), COX, reduced (GSH) and oxidized (GSSG) glutathione, or metabolic rate. This treatment resulted in great compensatory increases in SOD (to 250-460% of controls) and glutathione reductase (GR) (to 200%) which are possibly responsible for the lack of increase of in vivo and in vitro liver peroxidation and for the absence of changes in survival rate. The comparison of these results with previous data from other species suggests the possibility that decreases in antioxidant capacity in old age are restricted to animal species with high metabolic rates. Nevertheless, ageing can still be due to the continuous presence of small concentrations of O2 radicals in the tissues throughout life in animals with either high or low metabolic rates, because radical scavenging can not be 100% effective. Compensatory homeostasis among antioxidants seems to be a general phenomenon in different species.

Aging↗

PubMed1990

Changes on cerebral antioxidant enzymes, peroxidation, and the glutathione system of frogs after aging and catalase inhibition.

The five major antioxidant enzymes, glutathione, and in vivo or in vitro stimulated (Fe(++)-ascorbate) peroxidation were similar in old and young Rana perezi frogs. Long-term (2.5 months) treatment with aminotriazole strongly decreased cerebral catalase (CAT) activity and increased in vivo but not in vitro peroxidation in the brain. This suggests that the increase in endogenous brain peroxidation after CAT inhibition is due to an increased free-radical attack on cerebral membranes, and not to a possible increase in their sensitivity to peroxidative damage. The increase of in vivo peroxidation is especially remarkable taking into account the low levels of CAT present in the vertebrate brain. On the other hand, these changes were not accompanied by any effect on the survival of the animals. Comparison of these results with those obtained in other species suggests the possibility that O2-free radicals be of minor importance in relation to brain aging in animals with low rates of oxygen consumption.

Aging↗

PubMed1990

Lung antioxidant enzymes, peroxidation, glutathione system and oxygen consumption in catalase inactivated young and old Rana perezi frogs.

In the lung of Rana perezi no differences as a function of age have been found for any of the five major antioxidant enzymes, reduced (GSH), oxidized (GSSG) or glutathione ratio (GSSG/GSH), oxygen consumption (VO2) and for in vivo or in vitro stimulated tissue peroxidation. This frog shows a moderate rate of oxygen consumption and a life span substantially longer than that of rats and mice. Chronic (2.5 months) catalase depletion in the lung did not affect survival or any additional antioxidant enzyme, GSH, GSSG or in vivo and in vitro lung peroxidation in any age group. Only the GSSG/GSH ratio and the VO2 were elevated in catalase depleted old but not young frogs. After comparison of these results with those obtained in other animal species by other authors we suggest the possibility that decreases in antioxidant capacity in old age be restricted to species with high basal metabolic rates. Nevertheless, scavenging of oxygen radicals can not be 100% effective in any species. Thus, aging can still be due to the continuous presence of small concentrations of O2 radicals in the tissues throughout the life span in animals with either high or low metabolic rates.

Aging↗

PubMed1990

Aminotriazole effects on lung and heart H2O2 detoxifying enzymes and TBA-RS at two pO2.

In order to clarify the physiological role in vivo of H2O2-detoxifying enzymes at low and high levels of O2 tension we studied catalase (CAT), glutathione peroxidases (GP), and in vivo peroxidation (TBA-RS) in the lung and heart of Rana perezi frogs chronically treated with hyperoxia, aminotriazole (AT) -a CAT inhibitor-, or both. Hyperoxia did not change CAT, GP or TBA-RS. Aminotriazole caused an almost complete depletion of CAT, a 30% decrease of GP and a 132% (lung) to 200% (heart) increase of TBA-RS. Changes similar to these were found in the group treated with AT in hyperoxia. No mortality or changes in total or organ weight occurred in the experimental groups. Main conclusions are: (1) The maximal hyperoxia tolerance showed by frogs among vertebrates does not need antioxidant enzyme induction from lung or heart and is probably related to the presence of high constitutive levels of GP in relation to metabolic rate. (2) Even in normoxia the tissues present significant amounts of H2O2, and CAT is needed to avoid oxidative damage. GP does not compensate its absence. The implications of these results in relation to oxygen toxicity in man is discussed.

Amitrole↗

PubMed1989

Catalase is needed to avoid tissue peroxidation in Rana perezi in normoxia.

1. In order to clarify the relative role of catalase (CAT) and glutathione peroxidases (GSH-Px) at normal and high O2 tensions, Rana perezi frogs were chronically treated with aminotriazole (AT), hyperoxia, or both. 2. A 100% survival was observed with both treatments. Hyperoxia increased liver catalase and kidney TBA-RS and decreased GSH-Px. 3. AT caused quantitatively higher alterations than hyperoxia in both organs: CAT was depleted, TBA-RS increased (114% in kidney) and GSH-Px decreased. 4. It is concluded that in Rana perezi (a) CAT, in spite of its much higher KM and Vmax in relation to GSH-Px, is needed to avoid oxidative stress even in normoxia; (b) normoxic tissues have significative amounts of H2O2; (c) GSH-Px does not compensate the lack of CAT.

Amitrole↗

PubMed1988

Effect of hyperoxia acclimation on catalase and glutathione peroxidase activities and in vivo peroxidation products in various tissues of the frog Rana ridibunda perezi.

Among vertebrates, adult amphibians are known to be especially tolerant to exposure to high environmental oxygen tensions. To clarify the basis for this high O2 tolerance, adult Rana ridibunda perezi frogs were acclimated for 15 days to water-air phases with either 149 mm Hg O2 (normoxia) or 710 mm Hg O2 (hyperoxia). At the end of the acclimation, various morphometric and biochemical parameters related to oxidative stress were measured in seven organs and tissues. Hyperoxia acclimation did not change either the total weight of the animals or the total and relative wet weights of the organs studied, except for the brain, which showed weight increases in the hyperoxic group. In vivo tissue peroxidation increased in the kidney; decreased in the skeletal muscle and skin; and did not change in the liver, lung, brain, and heart after hyperoxic exposures. Whereas liver, lung, and skin showed glutathione peroxidase (GSH-Px) activities with both cumene hydroperoxide (cumene-OOH) and H2O2 as substrates, skeletal muscle only showed H2O2 GSH-Px activity. Hyperoxia acclimation did not change either catalase (CAT) or GSH-Px activities in any organ, except for the liver in which CAT activity was induced by hyperoxia. Thus hyperoxia tolerance in this species does not need the induction of H2O2-detoxifying enzymes in the majority of the organs. It is suggested that the high O2 tolerance of this amphibian species is related to its comparatively high constitutive GSH-Px activities.

Adaptation, Physiological↗

PubMed1988

Physiological significance of catalase and glutathione peroxidases, and in vivo peroxidation, in selected tissues of the toad Discoglossus pictus (Amphibia) during acclimation to normobaric hyperoxia.

1. Various parameters related to oxidative stress were measured in adult Discoglossus pictus acclimated for 15 days to either normoxia or hyperoxia (PO2 = 710 mmHg). 2. Total weight of the toads and total and relative wet weight of liver, kidneys, lungs and heart were not changed by hyperoxic acclimation. 3. In vivo tissue peroxidation increased in lung, decreased in skeletal muscle, and was not changed in liver, kidney, heart and skin after hyperoxic exposure. 4. Hyperoxic acclimation increased catalase activities in the lung, liver, kidney and heart but not in skeletal muscle and skin. 5. Liver showed higher GSH-peroxidase activity with cumene-OOH than with H2O2 as substrate, whereas lung, skeletal muscle and skin presented similar GSH-peroxidase activities with both substrates. 6. GSH-peroxidase activities did not change between hyperoxic and normoxic animals in liver, lung, skeletal muscle and skin. 7. These results show that catalase, not GSH-peroxidase, is the principal H2O2 detoxifying enzyme involved in the adaptation of D. pictus to hyperoxia.

Adaptation, Physiological↗

PubMedDate not supplied

A comparative study of free radicals in vertebrates--I. Antioxidant enzymes.

1. Five antioxidant enzymes and cytochrome oxidase were measured in three vital organs of seven animal species of different vertebrate classes. 2. Minimal superoxide dismutase activities were found in the brain of homeotherms and in the lung of amphibia. Catalase (CAT) was maximal in liver and minimal in brain. 3. Possession of both Se dependent and independent glutathione peroxidase (GPx) is widespread in vertebrate organs. Similarities in tissue distribution were found among enzymes which use hydroperoxides (Se and non-Se GPx and CAT) or glutathione (both GPx and glutathione reductase) as substrates. 4. The results also suggest that the high aerobic capacity of the liver strongly influences the activities of the antioxidant enzymes in this tissue across vertebrate species, whereas other factors such as tissue pO2 can be more important in the lung.

Amphibians↗

PubMedDate not supplied

A comparative study of free radicals in vertebrates--II. Non-enzymatic antioxidants and oxidative stress.

1. The three main non-enzymatic endogenous soluble antioxidants and three estimators of oxidative stress were measured in the liver, lung and brain of seven animal species of different vertebrate classes. 2. The more concentrated antioxidant was GSH, followed by ascorbate and finally by uric acid. Liver showed higher levels of GSH and uric acid than the other two organs in the majority of the species. 3. GSSG/GSH ratio was highest in lung, probably due to the high pO2 prevalent in the tissue. Nevertheless, this did not result in higher tissue peroxidation, suggesting that the lung antioxidants are capable of coping with a high tissue pO2. 4. Tissue peroxidation was maximal in the brain when assayed by the TBA test, but this was not confirmed by HPLC of malondialdehyde (MDA). HPLC resulted in much lower MDA values than TBA.

Amphibians↗

PubMedDate not supplied

Caloric and carbohydrate restriction in the kidney: effects on free radical metabolism.

Carbohydrate restriction and caloric restriction (60% restriction of calories in relation to controls in both cases) were imposed on OF1 mice during 8 weeks in their growing phase. The three groups of animals ingested the same amount of vitamins and minerals. Kidney ascorbate strongly decreased in both restriction groups. Nevertheless, global caloric restriction significantly increased kidney antioxidant glutathione (GSH)/oxidized glutathione (GSSG) ratio, a sign of a reduced kidney oxidative stress. Increased glutathione peroxidase and cytochrome oxidase activities and decreased in vivo peroxidation were found in the kidney when the restriction was performed by substituting carbohydrates by nonnutritive bulk. No significant changes were observed for superoxide dismutase, catalase, glutathione reductase, glutathione, uric acid, malondialdehyde (HPLC), or in vitro sensitivity to peroxidation in the kidney. The results, reported for the first time in this tissue, show that short-term caloric restriction can increase the capacity for enzymatic decomposition of hydroperoxides and can decrease oxidative stress in the kidney, thus suggesting a role for free radical metabolism in the caloric restriction phenomenon.

Animals↗

PubMedDate not supplied

Effect of early maternal adrenalectomy on antioxidant enzymes, GSH, ascorbate, and uric acid in the rat fetal lung at term.

Previous studies have shown that the increase of the enzymatic antioxidant defense that takes place in the fetal rat lung at the end of gestation can be accelerated by the synthetic glucocorticoid dexamethasone and diminished by metyrapone, a blocker of glucocorticoid synthesis. Since it is known that the fetal adrenal does not start to synthesize corticosterone until the last 20% of gestation, pregnant rats were bilaterally adrenalectomized on the first day of gestation in order to clarify the role of the endogenous maternal hormone on the development of the enzymatic and nonenzymatic antioxidant systems of fetal lung. This early adrenalectomy did not change fetal lung catalase, glutathione peroxidase, glutathione reductase, cytochrome oxidase, GSH, ascorbate, and uric acid at term. The presence of the maternal glands is not essential for lung antioxidant development in the fetus and that the stimulus of fetal corticosterone during the last 20% of gestation is enough to achieve a normal maturation of the fetal lung enzymatic and nonenzymatic antioxidant systems.

Adrenal Glands↗