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Biomedical subjects

G Barja

Publications and source records attributed to G Barja.

At least 55 records · Page 3Linked to original sources
PubMed1996

Low fatty acid unsaturation protects against lipid peroxidation in liver mitochondria from long-lived species: the pigeon and human case.

Birds have a much higher maximum longevity (MLSP) than mammals of similar metabolic rate. Recent data showed that pigeon mitochondria produce oxygen radicals at a rate much slower than rat mitochondria, in spite of showing similar levels of oxygen consumption (Free Rad. Res., 21 (1994) 317-328). Since oxidative damage from and to mitochondria seems important in relation to aging and longevity, and mitochondrial membranes are situated at the place where oxygen radicals are generated, we studied protein and lipid peroxidation and fatty acid composition of the three main membrane phospholipids of liver mitochondria from rats (MLSP = 4 years) and pigeons (MLSP = 35 years). It was found that pigeon mitochondria show lower levels of fatty acid unsaturation than rat mitochondria in the three lipid fractions, mainly due to a substitution of highly unsaturated fatty acids (20:4 and 22:6) by linoleic acid (18:2), and that these mitochondria are more resistant to lipid peroxidation. Previous research has also obtained exactly the same major difference in fatty acid composition in human mitochondria when compared to those of rat. Thus, present information suggests that the liver mitochondrial membranes of especially long-lived species show both a low level of free radical production and a low degree of fatty acid unsaturation as important constitutive protective traits to slow down aging.

Animals↗
PubMed1996

Effect of dietary vitamin E levels on fatty acid profiles and nonenzymatic lipid peroxidation in the guinea pig liver.

Guinea pigs were fed for five weeks with three diets containing different levels of vitamin E: LOW (but nondeficient, 15 mg of vitamin E/kg diet), MEDIUM (150 mg/kg diet), and HIGH (1,500 mg/kg diet). Dietary vitamin E supplementation did not change oxidative stress indicators in the hydrophilic compartment but increased liver alpha-tocopherol in a dose-dependent way and strongly decreased sensitivity to nonenzymatic in vitro liver lipid peroxidation. This last effect was already observed in group MEDIUM, and no further decrease in in vitro lipid peroxidation occurred from group MEDIUM to group HIGH. The protective effect of vitamin E against in vitro lipid peroxidation was observed even though an optimum dietary concentration of vitamin C for this animal model was present in the three different vitamin E diets. Both HIGH and LOW vitamin E decreased percentage fatty acid unsaturation in all phospholipid fractions from membrane origin in relation to group MEDIUM. The results, together with previous information, show that both vitamin E and vitamin C at intermediate concentrations are needed for optimal protection against lipid peroxidation and loss of fatty acid unsaturation even in normal nonstressful conditions. These protective concentrations are higher than those needed to avoid deficiency syndromes.

Animals↗
PubMed1996

Endotoxin depletes ascorbate in the guinea pig heart. Protective effects of vitamins C and E against oxidative stress.

The effect of acute endotoxin-induced septic shock on myocardium oxidative stress after low or high vitamin C and/or E dietary supplementation was studied in guinea pigs, laboratory animals which, like human, do not have capacity for ascorbate synthesis. Neither the antioxidant enzymes or GSH were modified by endotoxin and vitamin treatments. Vitamin E showed a strong capacity to protect the myocardium against both enzymatic and non-enzymatic lipid peroxidation even in the presence of endotoxin. Vitamin C supplementation increased heart ascorbate whereas endotoxic shock totally depleted the heart ascorbate of vitamin C supplemented animals without changing vitamin E. Endotoxin significantly increased myocardium uric acid, a marker of ischemia induced oxidative stress, in animals fed with low vitamin C levels. This increase was totally prevented in vitamin C supplemented, but not in vitamin E supplemented animals. Strongly depressed levels of plasma vitamin C have been recently described in sepsis in human patients. The results suggest that ascorbate is a primary antioxidant target in the heart of endotoxin treated mammals lacking the capacity to synthesize ascorbate and that ascorbate can have a protective value against endotoxin-induced free radical damage in the myocardium. Implications of these results for the possible preventive role of vitamin C in humans during sepsis are discussed.

Analysis of Variance↗
PubMed1996

Increase in heart glutathione redox ratio and total antioxidant capacity and decrease in lipid peroxidation after vitamin E dietary supplementation in guinea pigs.

Dietary treatment with three diets differing in vitamin E, Low E (15 mg of vitamin E/kg diet), Medium E (150 mg/kg), or High E (1,500 mg/kg), resulted in guinea pigs with low (but nondeficient), intermediate, or high heart alpha-tocopherol concentration. Neither the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and reductase, nor the nonenzymatic antioxidants, GSH, ascorbate, and uric acid were homeostatically depressed by increases in heart alpha-tocopherol. Protection from both enzymatic (NADPH dependent) and nonenzymatic (ascorbate-Fe2+) lipid peroxidation was strongly increased by vitamin E supplementation from Low to Medium E whereas no additional gain was obtained from the Medium E to the High E group. The GSH/GSSG and GSH/total glutathione ratios increased as a function of the vitamin E dietary concentration closely resembling the shape of the dependence of heart alpha-tocopherol on dietary vitamin E. The results show the capacity of dietary vitamin E to increase the global antioxidant capacity of the heart and to improve the heart redox status in both the lipid and water-soluble compartments. This capacity occurred at levels six times higher than the minimum daily requirement of vitamin E, even in the presence of optimum dietary vitamin C concentrations and basal unstressed conditions. The need for vitamin E dietary supplementation seems specially important in this tissue due to the low constitutive levels of endogenous enzymatic and nonenzymatic antioxidants present of the mammalian heart in comparison with those of other internal organs.

Animals↗
PubMed1996

Vitamin E decreases urine lipid peroxidation products in young healthy human volunteers under normal conditions.

An experimental study on the effects of supplementation with antioxidant vitamins on urine lipid peroxidation products was performed in 21 young healthy men. The subjects ingested placebo, 1 g of vitamin C, or 100 mg of vitamin E per day just after the midday meal during 30 days. Urine samples were obtained 0, 15 and 30 days after the beginning of the study. These samples were analyzed by spectrophotometry or fluorometry after reaction with thiobarbituric acid. Prescan fluorometric studies of the thiobarbituric acid reactive substances in both malondialdehyde standards and urine samples indicated 503 nm and 548 nm as optimum excitation and emission wavelengths. The fluorescence measurements proved to be superior both in terms of selectivity and capacity of detection of antioxidant effects in relation to spectrophotometry. Identical emission peaks were obtained with malondialdehyde standards and urine samples, showing the specificity of the fluorometric method. When measured by fluorometry, the urine of the subjects supplemented with vitamin E showed significantly and progressively smaller lipid peroxidation products as the time of supplementation increased, reaching a 27% decrease at the end of the longitudinal trial. The results indicate the usefulness of the fluorescent measurement of urine thiobarbituric acid reactive substances to easily and rapidly detect variations in whole body oxidative stress in humans. They also show the capacity of safe vitamin E dietary doses to decrease endogenous oxidative stress in healthy humans routinely performing their normal activities.

Adult↗
PubMed1996

Phospholipid hydroperoxides and lipid peroxidation in liver and plasma of ODS rats supplemented with alpha-tocopherol and ascorbic acid.

Forty-five mutant male ODS rats, unable to synthesize ascorbic acid, were fed nine diets containing 5, 50 or 250 mg of vitamin E/kg diet and 150, 300 or 900 mg of vitamin C/kg diet for 21 days. The concentrations of vitamins C and E increased in liver and plasma in relation to the level of these vitamins in the diet. Vitamin C dietary supplementation increased the plasma vitamin E content at low levels of vitamin E intake, supporting the concept of an in vivo synergism between both antioxidant vitamins. Vitamin C, at the dietary levels studied, did not affect the lipid peroxidation. Vitamin E decreased liver and plasma endogenous levels of thiobarbituric acid-reactive substances and liver sensitivity to non-enzymatic lipid peroxidation. This was confirmed by a highly specific assay of lipid hydroperoxides using high performance liquid chromatography with chemiluminescence detection. The hepatic concentration of both phosphatidylcholine and phosphatidylethanolamine hydroperoxides decreased as the vitamin E content of the diet increased. The results show for the first time the capacity of vitamin E to protest against peroxidation of major phospholipids in vivo under basal unstressed conditions.

Animals↗
PubMed1995

Vitamin E protects guinea pig liver from lipid peroxidation without depressing levels of antioxidants.

Oxidative stress is considered a pathogenic factor in many disorders. The capacity of dietary vitamin E to increase global antioxidant capacity and to decrease lipid peroxidation was studied in the guinea pig, an animal that cannot synthesize ascorbate. Male guinea pigs were subjected for 5 weeks to three diets differing in vitamin E content in the presence of optimum levels of vitamin C: group 15 (15 mg vitamin E/kg diet), group 150 (150 mg/kg), and group 1500 (1500 mg/kg). Hepatic vitamin E increased in the three groups in relation to the level of vitamin E in the diet. The increase in vitamin E between groups 15 and 150 was accompanied by a reduction in sensitivity to enzymatic lipid peroxidation. This did not occur between groups 150 and 1500. The different liver vitamin E concentrations did not affect the antioxidant enzymes superoxide dismutase, catalase, GSH-peroxidase and GSH-reductase, nor the non-enzymatic antioxidants vitamin C, GSH and ascorbate. It is concluded that dietary supplementation with vitamin E, at a level 6 times higher than the minimum daily requirement for guinea pigs, increases protection against hepatic lipid peroxidation without depressing endogenous antioxidant defences. Further increases in vitamin E to megadose levels did not provide additional protection from oxidative stress. The results also suggest that optimum levels of both vitamin C and vitamin E, simultaneously needed for protection against oxidative stress, are much higher than the minimum daily requirements.

Animals↗
PubMed1994

Longevity and antioxidant enzymes, non-enzymatic antioxidants and oxidative stress in the vertebrate lung: a comparative study.

It has been proposed that antioxidants can be longevity determinants in animals. However, no comprehensive study has been conducted to try to relate free radicals with maximum life span. This study compares the lung tissue of various vertebrate species--amphibia, mammals and birds--showing very different and well known maximum life spans and life energy potentials. The lung antioxidant enzymes superoxide dismutase, catalase, Se-dependent and non-Se-dependent glutathione peroxidases, and glutathione reductase showed significantly negative correlations with maximum life span. The same was observed for the lung antioxidants, reduced glutathione and ascorbate. It is concluded that a generalized decrease in tissue antioxidant capacity is a characteristic of longevous species. It is suggested that a low rate of free radical recycling (free-radical generation and scavenging) can be an important factor involved in the evolution of high maximum animal longevities. A low free-radical production could be responsible for a low rate of damage at critical sites such as mitochondrial DNA.

Animals↗
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

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↗