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Biomedical subjects

Jesús R Huertas

Publications and source records attributed to Jesús R Huertas.

15 recordsLinked to original sources

Age-related mitochondrial DNA deletion in rat liver depends on dietary fat unsaturation.

We fed male Wistar rats lifelong on virgin olive (rich in the monounsaturated oleic acid) or sunflower (rich in the polyunsaturated linoleic acid) oil-based diets. At 6 and 24 months, liver mitochondria were analyzed for a mitochondrial DNA (mtDNA) deletion, reactive oxygen species, antioxidants, and ultrastructural alterations. An aging-related increase in the relative amount of the deletion was observed for both dietary groups, being higher in animals fed sunflower oil. Oxidative stress was lower in virgin olive oil-fed animals. Aging led to higher superoxide dismutase, catalase, and glutathione peroxidase activities and increased alpha-tocopherol and coenzyme Q. Mitochondria from aged animals fed sunflower oil exhibited a lower number of cristae and a higher circularity. Results suggest that the age-related increase of the relative amount of deleted mtDNA depends on fat unsaturation. Moreover, the studied mtDNA deletion was correlated with mitochondrial oxidative stress and ultrastructural alterations.

Aging↗

Life-long supplementation with a low dosage of coenzyme Q10 in the rat: effects on antioxidant status and DNA damage.

Life-long low-dosage supplementation of coenzyme Q(10) (CoQ(10)) is studied in relation to the antioxidant status and DNA damage. Thirty-two male rats were assigned into two experimental groups differing in the supplementation or not with 0.7 mg/kg/day of CoQ(10). Eight rats per group were killed at 6 and 24 months. Plasma retinol, alpha-tocopherol, coenzyme Q, total antioxidant capacity and fatty acids were analysed. DNA strand breaks were studied in peripheral blood lymphocytes. Aging and supplementation led to significantly higher values for CoQ homologues, retinol and alpha-tocopherol. No difference in total antioxidant capacity was detected at 6 months but significantly lower values were found in aged control animals. Similar DNA strand breaks levels were found at 6 months. Aging led to significantly higher DNA strand breaks levels in both groups but animals supplemented with CoQ(10) led to a significantly lower increase in that marker. Aged rats showed significantly higher polyunsaturated fatty acids. This study demonstrates that lifelong intake of a low dosage of CoQ(10) enhances plasma levels of CoQ(9), CoQ(10), alpha-tocopherol and retinol. In addition, CoQ(10) supplementation attenuates the age-related fall in total antioxidant capacity of plasma and the increase in DNA damage in peripheral blood lymphocytes.

Aging↗

Coenzyme Q10 protects from aging-related oxidative stress and improves mitochondrial function in heart of rats fed a polyunsaturated fatty acid (PUFA)-rich diet.

Coenzyme Q(10) supplementation on age-related changes in oxidative stress and function of heart mitochondria in rats fed a polyunsaturated fatty acid (PUFA)-rich diet was investigated. Two groups of rats were fed for 24 months on a PUFA-rich diet, differing in supplementation or not with coenzyme Q(10). Animals were killed at 6, 12, or 24 months. Fatty-acid profile, hydroperoxides, alpha-tocopherol, coenzyme Q, catalase and glutathione peroxidase activities, and cytochromes a+a(3), b, c+c(1) and cytochrome c oxidase activity were measured. Coenzyme Q(10)-supplemented animals showed lower hydroperoxide levels; higher content and/or activity of alpha-tocopherol, coenzyme Q, and catalase; and a slightly lower decrease in mitochondrial function. According to that, previously reported positive effects of coenzyme Q supplementation on the life span of rats fed a PUFA-rich diet might be a consequence, at least in part, of a lower oxidative stress level and perhaps, to a minor extent, of a smaller decrease in mitochondrial function.

Aging↗

Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet.

This study investigates the usefulness of a long-term supplementation with coenzyme Q(10) in rats from the point of view of lifespan, DNA double-strand breaks and to assess whether this supplementation might attenuate oxidative alterations related to PUFA-rich diets, which would allow to preserve beneficial aspects of PUFA on health avoiding their deleterious aspects. Supplemented animals showed higher concentration of coenzyme Q(10) in liver mitochondria, lower levels of DNA double-strand breaks in peripheral blood lymphocytes. Animals supplemented on coenzyme Q reached a significantly higher mean life span (11,7% higher, i.e. 2,5 months) and a significantly higher maximum life span (24% higher, i.e. 6 months) than non-supplemented animals. These results suggest that a long-term supplementation with a small dosage of coenzyme Q(10) might represent a good anti-aging therapy in rats fed on a PUFA-based diet.

Aging↗

Dietary fat type (virgin olive vs. sunflower oils) affects age-related changes in DNA double-strand-breaks, antioxidant capacity and blood lipids in rats.

This study was designed to investigate the possible effect on DNA double-strand breaks, antioxidant capacity and blood lipids of feeding rats lifelong with two different dietary fat sources: virgin olive oil (rich in the monounsaturated oleic acid) or sunflower oil (rich in the polyunsaturated linoleic acid). No changes in mean or maximal lifespan were observed. Overall, aging led to increased levels of plasma cholesterol, triglycerides, phospholipids, total lipids, polyunsaturated fatty acids and DNA double-strand breaks. All these parameters were higher in animals fed on sunflower oil diet. Aging diminished total antioxidant capacity with both diets, but in a lower extension for virgin olive oil diet. A very good inverse correlation (r= -0.715; P < 0.01, for sunflower oil group and r= -0.535; P < 0.01 for virgin olive oil group) between DNA damage and total antioxidant capacity was found. These results allow to conclude that dietary fat type should be considered in studies on aging, since the intake of oils with different polyunsaturation levels directly modulates total antioxidant capacity of plasma, DNA damage to peripheral blood lymphocytes and lead to important changes at the lipid metabolism level. In the present study best results were found after intake of virgin olive oil, which suggest the possible use of that edible oil to provide a healthier aging.

Aging↗

Dietary fat (virgin olive oil or sunflower oil) and physical training interactions on blood lipids in the rat.

OBJECTIVE: We investigated whether the intake of virgin olive oil or sunflower oil and performance of physical exercise (at different states) affect plasma levels of triacylglycerols, total cholesterol, and fatty acid profile in rats. METHODS: The study was carried out with six groups of male rats subjected for 8 wk to a diet based on virgin olive oil (three groups) or sunflower oil (three groups) as dietary fat. One group for each diet acted as sedentary control; the other two groups ran in a treadmill for 8 wk at 65% of the maximum oxygen consumption. One group for each diet was killed 24 h after the last bout of exercise and the other was killed immediately after the exercise performance. Triacylglycerols, total cholesterol, and fatty acid profile were analyzed in plasma. Analysis of variance was used to test differences among groups. RESULTS: Animals fed on virgin olive oil had lower triacylglycerol and cholesterol values. Physical exercise reduced these parameters with both dietary treatments. Fatty acid profile showed higher monounsaturated fatty acid proportion in virgin olive fed oil animals and a higher omega-6 polyunsaturated fatty acid proportion in sunflower oil fed animals. Physical exercise reduced the levels of monounsaturated fatty acids with both diets and increased the proportions of omega-3 polyunsaturated fatty acids. CONCLUSIONS: Results from the present study supported the idea that physical exercise and the intake of virgin olive oil are very good ways of reducing plasma triacylglycerols and cholesterol, which is desirable in many pathologic situations. Concerning findings on fatty acid profile, we had results similar to those of other investigators regarding the effect of different sources of dietary fat on plasma. The most interesting results came from the effect of physical exercise, with significant increases in the levels of omega-3 polyunsaturated fatty acids, which may contribute to the antithrombotic state and lower production of proinflammatory prostanoids attributed to physical exercise.

Animals↗

Aging-related oxidative stress depends on dietary lipid source in rat postmitotic tissues.

We investigate mitochondrial-lipid peroxidation of mitotic (liver) and postmitotic (heart and skeletal muscle) tissues of rats fed lifelong on two different lipid sources: virgin olive oil (monounsaturated fatty acids) and sunflower oil (n - 6 polyunsaturated fatty acids). Two groups of 80 rats each were fed over 24 months on a diet differing in the lipid source (virgin olive oil or sunflower oil). Twenty rats per group were killed at 6, 12, 18, and 24 months; liver, heart, and skeletal muscle mitochondria were isolated and the lipid profile, hydroperoxides, vitamin E, and ubiquinone as well as catalase activity measured. Lipid peroxidation was higher in postmitotic tissues, and sunflower oil led to a higher degree of polyunsaturation and peroxidation. The levels of alpha-tocopherol adapted to oxidative stress and preferentially accumulated during aging in heart and skeletal muscle. In conclusion, the type of dietary fat should be considered in studies on aging, since oxidative stress is directly modulated by this factor. This study confirms that postmitotic tissues are more prone to oxidative stress during aging and proposes a hypothesis to explain this phenomenon.

Aging↗

Oxidative stress is evident in erythrocytes as well as plasma in patients undergoing heart surgery involving cardiopulmonary bypass.

OBJECTIVE: The aim of this study was to analyse the level and progression of oxidative stress, in both plasma and erythrocytes, during heart surgery involving cardiopulmonary bypass. MATERIALS AND METHODS: Twenty two patients undergoing cardiac surgery and considered to present a high/severe level of surgical risk were selected. We took five blood samples at different times during the cardiac surgery and analysed TBARS, alpha-tocopherol, coenzyme Q and retinol in plasma and TBARS (baseline levels and induced by Fe2+-ascorbate oxidation), alpha-tocopherol, coenzyme Q and catalase, superoxide dismutase and gluthatione peroxidase activity in erythrocytes. RESULTS: Plasma results shown a decrease in both alpha-tocopherol and retinol concentration after starting CPB with respect to the reference level (13.6 +/- 1.5 nmol ml(-1) vs. 22.0 +/- 3.0 nmol ml(-1) and 1.2 +/- 0.1nmol ml(-1) vs. 1.8 +/- 0.2 nmol ml(-1), respectively (p < 0.05)). In comparison, in erythrocytes, all antioxidants, both enzymatic and non-enzymatic, increased in activity or concentration after starting CPB. Erythrocyte TBARS, both baseline levels and induced levels, followed a similar pattern, with an increase after starting CPB with respect to the reference level (3.9 +/- 0.6 nmol mg(-1) of protein vs. 2.3 +/- 0.2 nmol mg(-1) of protein and 10.6 +/- 0.8 nmol mg(-1) of protein vs. 6.7+/- 0.6 nmol mg(-1) of protein, respectively (p < 0.05)). CONCLUSION: These results reveal an increase in oxidative stress after CPB, both in plasma and erythrocytes, and although the organism is capable of attenuating this stress by means of various antioxidative defence mechanisms, there is an increased possibility of post-CPB complications and thus of mortality.

Cardiopulmonary Bypass↗

Oxidative stress in erythrocytes from premature and full-term infants during their first 72 h of life.

OBJECTIVE: The aim of this study was to evaluate the extent of lipid peroxidation and the response of the enzymatic and non-enzymatic antioxidant defence system in erythrocytes from full-term and premature infants at birth, after 3 and after 72 h of life. STUDY DESIGN: Twenty infants were selected and divided in two groups according to their gestational age. Blood samples were taken at birth, at 3 and at 72 h of life, erythrocytes were isolated and the following parameters were measured: fatty-acid profile, coenzyme Q, alpha-tocopherol, hydroperoxides and the activity of the antioxidant enzymes catalase, superoxide dismutase (SOD) and cytosolic glutathione peroxidase (cGPx). RESULTS: For the three studied periods, several differences between full-term and premature infants were found. Premature children showed a higher concentration of hydroperoxides, a lower level of alpha-tocopherol and lower SOD and cGPx activity (except for cGPx at birth). Moreover, n-3 polyunsaturated fatty-acids percentages (essential for good neonatal development) were higher in full term children throughout all the study. CONCLUSION: Results suggest a strong imbalance between oxidants and antioxidants in premature infants during their first 72 h of life, a situation which could lead to several pathologies. Therefore, further research is needed, including possible nutritional intervention (with antioxidant therapy, supplementation of essential fatty acids and other dietary constituents) before and after birth.

Antioxidants↗

Antioxidant nutrients and adriamycin toxicity.

The anthracycline antibiotic adriamycin (doxorubicin) is one of the most effective chemotherapeutic agents against a wide variety of cancers. However, its use is seriously limited by the development in the heart of acute and chronic toxic effects. Mechanisms of action and toxicity of adriamycin are briefly revised in this review. Among followed strategies to attenuate adriamycin toxicity are dosage optimisation, synthesis and use of analogues or combined therapy with antioxidants. The most promising results come from the combination of the drug delivery together with an antioxidant in order to reduce oxidative stress. Many antioxidants have been assayed with very different results. Among these molecules, metal ions chelators and low-molecular-mass agents that scavenge reactive oxygen species and that are synthesised in vivo have been widely studied. However, the present review will be exclusively focused on the antioxidants that are derived from the diet, in particular the role of vitamin E, vitamin C, vitamin A, coenzyme Q, flavonoids, antioxidant components of virgin olive oil and selenium.

Animals↗

Dietary oils high in oleic acid but with different unsaponifiable fraction contents have different effects in fatty acid composition and peroxidation in rabbit LDL.

OBJECTIVE: We investigated the influence of different edible oils high in oleic acid but with different unsaponifiable fractions on the fatty acid composition and lipid peroxidation in plasma and low-density lipoprotein (LDL) in rabbits. METHODS: Thirty-two rabbits were randomly assigned to four groups of eight animals. For 8 wk each group was fed a semisynthetic isoenergetic diet that differed by lipid source (Picual virgin olive oil, Picual virgin olive oil that had been subjected to an exhaustive process of washing, Arbequina virgin olive oil, and sunflower oil high in oleic acid). We analyzed the fatty acid profile, thiobarbituric acid reactive substances, alpha-tocopherol, coenzyme Q, and retinol in plasma and the fatty acid profile, hydroperoxides, alpha-tocopherol, and coenzyme Q in LDL. RESULTS: The two varieties of virgin olive oil behaved differently from the high-oleic sunflower oil, and the effect of the different ratios of oleic acid to linoleic acid in the lipid sources on fatty acid composition in plasma and LDL was significant. With regard to oxidative stress, LDL in the group that ingested the lipid sources with the greatest amount of phenolic compounds showed the highest level of antioxidants (alpha-tocopherol and coenzyme Q; P < 0.05) and the lowest susceptibility to lipid peroxidation (P < 0.05). CONCLUSION: This study provides evidence in vivo of the considerable antioxidant capacity of the phenolic fraction of virgin olive oil in rabbit LDL and the important role that this unsaponifiable fraction can play in the overall antioxidant benefit attributed to these oils. However, these effects depend on the phenolic content of the oil.

Animals↗

Feeding fried oil changes antioxidant and fatty acid pattern of rat and affects rat liver mitochondrial respiratory chain components.

Fat frying is a popular food preparation method but several components like antioxidant vitamins could be lost due to oxidation and some others with toxic effects could appear. Because of such large consumption of frying oils, the effect of high temperatures on the oils is of major concern both for product quality and nutrition, taking into account that dietary fat source deeply influences several biochemical parameters, especially of mitochondrial membranes. Virgin olive oil possesses specific features for modulating the damages occurred by endogenous and exogenous oxidative stress being particularly rich in antioxidant molecules. We evaluated the extent of modifications suffered by virgin olive oil following a short-time deep fat frying procedure: vitamin E and phenolic compound as well as total antioxidant capacity (measured by ESR) decreased, while polar compounds increased. The intake of such an altered oil mainly affected the hydroperoxide and TBARS contents of mitochondrial membranes which were enhanced after the dietary treatments. Also, several mitochondrial respiratory chain components (Coenzyme Q, cytochrome b, c + c1, and a + a3) were affected.

Animals↗

Ageing-related tissue-specific alterations in mitochondrial composition and function are modulated by dietary fat type in the rat.

This study investigated the way in which feeding rats with two fat sources (olive or sunflower oils) affected electron-transport components and function of mitotic (liver) and postmitotic (heart and skeletal muscle) tissues during ageing. Rats adapted the mitochondrial-membrane-lipid profile to dietary fat throughout the study, suggesting that the benefits to eat either of the two fats might be maintained lifelong. Liver was more resistant to dietary changes and ageing than heart and skeletal muscle, which showed higher levels of coenzyme Q, cytochrome b, and cytochrome a + a3 with ageing and lower cytochrome c oxidase and complex IV turnover. Dietary fat differentially modulated the response of tissues during ageing, with sunflower oil leading to the highest levels of coenzyme Q and cytochromes b and a + a3. Since high levels of cytochrome b have been related to increased age, it could be hypothesized that olive oil could lead to less aged mitochondria.

Aging↗

The intake of fried virgin olive or sunflower oils differentially induces oxidative stress in rat liver microsomes.

The effects of non-fried and fried virgin olive and sunflower oils on rat liver microsomal compositional features have been investigated. In addition, plasma antioxidants (alpha-tocopherol and ubiquinone 9) were investigated as well as the possible oxidative modifications suffered by virgin olive and sunflower oils during the frying process. The frying process decreased the content of alpha-tocopherol and phenolics in the oils and increased total polar materials. Sunflower oil was affected to a greater extent than olive oil. In rats, the intake of fried oil led to higher levels of lipid peroxidation and a lower concentration of plasma antioxidants. Microsomal fatty acid and antioxidant profiles were also altered. It seems that a strong relationship exists between the loss of antioxidants and the production of toxic compounds in the oils after frying and the extent of the peroxidative events in microsomes, which were also different depending on the fat source. The highly unsaturated sunflower oil was less resistant to the oxidative stress produced by frying and led to a higher degree of lipid peroxidation in liver microsomes in vivo than virgin olive oil.

Animals↗

Structural damage induced by peroxidation may account for functional impairment of heavy synaptic mitochondria.

Coenzyme Q distribution, as well as respiratory chain features, in rat brain mitochondria depend on mitochondrial subpopulation, brain region and age. Heavy mitochondria (HM) usually display the lowest content of respiratory components and the lowest enzymatic activities and it has been suggested that they represent the oldest mitochondrial population. In this study, we confirmed that HM are considerably compromised in their structure. In fact, HM showed to have the highest hydroperoxide content and the most consistent modifications in their fatty acid pattern with wide loss of fatty acids (or part of them) in the phospholipid moiety. Such situation could explain the typical impairment of HM and could support the hypothesis that they represent an old mitochondrial population.

Age Factors↗