Biomedical subjects

S Cadenas

Publications and source records attributed to S Cadenas.

31 records · Page 2Linked to original sources

PubMed1994

A decrease of free radical production near critical targets as a cause of maximum longevity in animals.

A comprehensive study was performed on the brains of various vertebrate species showing different life energy potentials in order to find out if free radicals are important determinants of species-specific maximum life span. Brain superoxide dismutase, catalase, Se-dependent and independent GSH-peroxidases, GSH-reductase, and ascorbic acid showed significant inverse correlations with maximum longevity, whereas GSH, uric acid, GSSG/GSH, in vitro peroxidation (thiobarbituric acid test), and malondialdehyde (measured by HPLC), did not correlate with maximum life span. Superoxide dismutase, catalase, GSH-peroxidase, GSH and ascorbate results agree with those previously reported in various independent works using different animal species. GSSG/GSH, and true malondialdehyde (HPLC) results are reported for the first time in relation to maximum longevity. The results suggest that longevous species simultaneously show low antioxidant concentrations and low levels of in vivo free radical production (a low free radical turnover) in their tissues. The "free radical production hypothesis of aging" is proposed: a decrease in oxygen radical production per unit of O2 consumption near critical DNA targets (mitochondria or nucleus) increases the maximum life span of extraordinarily long-lived species like birds, primates, and man. Free radical production near these DNA sites would be a main factor responsible for aging in all the species, in those following Pearl's (Rubner's) metabolic rule as well as in those not following it.

Aging↗

PubMed1994

Dietary vitamin C decreases endogenous protein oxidative damage, malondialdehyde, and lipid peroxidation and maintains fatty acid unsaturation in the guinea pig liver.

Guinea pigs were fed during 5 weeks with three different levels of vitamin C in the diet: 33 (marginal deficiency), 660, or 13,200 mg of vitamin C per kg of diet. The group fed 660 mg of vitamin C/kg of diet showed strongly reduced levels of protein carbonyls (46% decrease), malondialdehyde (HPLC; 72% decrease), and in vitro production of TBARS (both stimulated with ascorbate-Fe2+ and with NADPH-ADP-Fe2+; 68% and 71% decrease), increased glutathione reductase activity, and increased vitamin C content (48 times higher) in the liver in relation to the group fed 33 mg/kg. The treatment with 660 mg of vitamin C/kg did not decrease any of the antioxidant defenses studied: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, GSH, vitamin E, or uric acid. Further supplementation with 13,200 mg vitamin C/kg also reduced protein and lipid peroxidation, but decreased hepatic glutathione reductase and uric acid and resulted in a lower body weight of the animals. Both low (33 mg/kg) and very high (13,200 mg/kg) levels of vitamin C decreased body weight, glutathione reductase, and unsaturation of fatty acids in membrane lipids. The results show that a diet supplying an amount of vitamin C 40 times higher than the minimum daily requirement to avoid scurvy increases the global antioxidant capacity and is of protective value against endogenous lipid and protein oxidation in the liver under normal nonstressful conditions.

Animals↗

PubMed1994

Effect of dietary vitamin C and catalase inhibition of antioxidants and molecular markers of oxidative damage in guinea pigs.

Guinea pigs were fed for five weeks with two diets with different levels of vitamin C, low (33 mg of Vit C/Kg diet) and high (13,200 mg of Vit C/Kg of diet). Catalase was inhibited with 3-amino-1,2,4-triazole (AT) in half of the animals from each dietary group. AT caused an almost complete depletion of liver catalase activity (90%) in both dietary groups. Vitamin C supplementation increased total glutathione peroxidase activity and tissue vitamin C level and decreased levels of protein carbonyls and malondialdehyde (MDA) in both treated and non-treated animals. This vitamin C supplementation did not change any of the other antioxidant defences studied. Our results show that dietary vitamin C supplementation increases global antioxidant capacity and decreases endogenous oxidative damage in the guinea pig liver under normal non-stressful conditions. This supports the protective value of dietary antioxidant supplementation.

Amitrole↗

PubMed1994

Low mitochondrial free radical production per unit O2 consumption can explain the simultaneous presence of high longevity and high aerobic metabolic rate in birds.

Birds are unique since they can combine a high rate of oxygen consumption at rest with a high maximum life span (MLSP). The reasons for this capacity are unknown. A similar situation is present in primates including humans which show MLSPs higher than predicted from their rates of O2 consumption. In this work rates of oxygen radical production and O2 consumption by mitochondria were compared between adult male rats (MLSP = 4 years) and adult pigeons (MLSP = 35 years), animals of similar body size. Both the O2 consumption of the whole animal at rest and the O2 consumption of brain, lung and liver mitochondria were higher in the pigeon than in the rat. Nevertheless, mitochondrial free radical production was 2-4 times lower in pigeon than in rat tissues. This is possible because pigeon mitochondria show a rate of free radical production per unit O2 consumed one order of magnitude lower than rat mitochondria: bird mitochondria show a lower free radical leak at the respiratory chain. This result, described here for the first time, can possibly explain the capacity of birds to simultaneously increase maximum longevity and basal metabolic rate. It also suggests that the main factor relating oxidative stress to aging and longevity is not the rate of oxygen consumption but the rate of oxygen radical production. Previous inconsistencies of the rate of living theory of aging can be explained by a free radical theory of aging which focuses on the rate of oxygen radical production and on local damage to targets relevant for aging situated near the places where free radicals are continuously generated.

Aerobiosis↗

PubMed1994

Effect of vitamin C on antioxidants, lipid peroxidation, and GSH system in the normal guinea pig heart.

Male guinea pigs were fed during 5 weeks with diets differing only in vitamin C content: low (33 mg/kg diet), medium (660 mg/kg), and high (13,200 mg/kg). Heart vitamin C was strongly dependent on dietary vitamin C and heart vitamin E showed a trend to increase as a function of the vitamin C level in the diet. The low vitamin C diet decreased body weight gain, food intake, and heart malondialdehyde without changing lipid peroxidation, whereas the high vitamin C increased oxidized glutathione and glutathione peroxidase and decreased body growth. A tendency to show higher levels of all the first-line antioxidants reduced glutathione, uric acid, superoxide dismutase, catalase, and glutathione peroxidase at extreme (high or low) dietary levels of vitamin C was observed. The guinea pig heart showed capacity for enzymatic but not for non-enzymatic in vitro lipid peroxidation. It is concluded that dietary vitamin C supplementation is able to increase the global antioxidant capacity of the heart tissue.

Animals↗

PubMed1993

Maximum life span in vertebrates: relationship with liver antioxidant enzymes, glutathione system, ascorbate, urate, sensitivity to peroxidation, true malondialdehyde, in vivo H2O2, and basal and maximum aerobic capacity.

In order to help clarify whether free radicals are implicated or not in the evolution of maximum life span (MLSP) of animals, a comprehensive study was performed in the liver of various vertebrate species. Strongly significant negative correlations against MLSP were found for hepatic catalase, Se-dependent and -independent glutathione peroxidases, and GSH, whereas superoxide dismutase, glutathione reductase, ascorbate, uric acid, GSSG/GSH, in vitro peroxidation (TBA-RS), and in vivo steady-state H2O2 concentration in the liver did not correlate with MLSP. Superoxide dismutase, catalase, glutathione peroxidase, and GSH results were in agreement with those independently reported by other authors, whereas the rest of our data are reported for the first time. Potential limitations arising from the use of animals of different vertebrate Classes were counterbalanced by the possibility to study animals with very different MLSPs and life energy potentials. Furthermore, the results agreed with previous data obtained using only mammals. Since liver GSSG/GSH, peroxidation, and specially H2O2 concentration were similar in species with widely different MLSPs, it is suggested that the decrease in enzymatic H2O2 detoxifying capacity of longevous species represents an evolutionary co-adaptation with a smaller in vivo rate of free radical generation. We propose the possibility that maximum longevity was increased during vertebrate evolution by lowering the rate of free radical recycling in the tissues.

Aerobiosis↗

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

Lung glutathione reductase induction in aging catalase-depleted frogs correlates with early survival throughout the life span.

A comprehensive experimental study on free radical-related parameters was performed in the lung throughout the life span of 220 initially young or old frogs. No age related differences were found transversely or longitudinally for lung superoxide dismutase, catalase, Se-dependent and -independent glutathione peroxidases, glutathione reductase, GSH, GSSG, or GSSG/GSH ratio. Continuous catalase depletion with aminotriazole led to glutathione reductase induction in the lung after 14.5 months of experimentation. This was accompanied by a great increase in survival rate of treated animals in relation to controls (especially in the old group). After 26.5 months of experimentation, glutathione reductase induction was lost and GSSG/GSH values tended to increase. This was followed by a 3-month long period of acute decrease in survival rate of treated animals. It is suggested that a high antioxidant/prooxidant balance is of protective value against causes of early death and can possibly be used in the future (when appropriately controlled) to increase the number of healthy years of the normal life span.

Aging↗

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↗

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↗