Jesús R. Huertas

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.

Tissue Specific Interactions of Exercise, Dietary Fatty Acids, and Vitamin E in Lipid Peroxidation

Both physical exercise and ingestion of polyunsaturated fatty acids that play an essential role in free radical-mediated damages cause lipid peroxidation. The intake of specific fatty acids can modulate the membrane susceptibility to lipid peroxidation. Data confirmed that liver, skeletal muscle, and heart have different capabilities to adapt their membrane composition to dietary fatty acids, the heart being the most resistant to changes. Such specificity affects membrane hydroperoxide levels that depend on the type of dietary fats and the rate of fatty acid incorporation into the membrane. Sedentary rats fed a monounsaturated fatty acid-rich diet (virgin olive oil) showed a higher protection of their mitochondrial membranes against peroxidation than sedentary rats fed a polyunsaturated fatty acid-rich diet (sunflower oil). Rats subjected to training showed higher hydroperoxide contents than sedentary animals, and exhaustive effort enhanced the aforementioned results as well as in vitro peroxidation with a free radical inducer. This study suggests that peroxide levels first depend on tissue, then on diet and lastly on exercise, both in liver and muscle but not in heart. Finally, it appears that alpha-tocopherol is a less relevant protective agent against lipid peroxidation than monounsaturated fatty acids.

Natural distribution and occurrence of coenzyme Q homologues

The knowledge of coenzyme Q levels in tissues, organs, and subcellular compartments is of outstanding interest. A wide amount of data regarding coenzyme Q distribution and occurrence was collected in the last decades; nevertheless the data are often hard to compare because of the different extraction methods and different analytical techniques used. We have undertaken a systematic study for detecting the ubiquinone content in subcellular compartments, cells, and whole-tissue homogenates by a previously standardized HPLC method performed after an extraction procedure identical for all samples. It was confirmed that the major coenzyme Q homologue in rat tissues is coenzyme Q9; however, it was pointed out that all the rodents samples tested contain more than one coenzyme Q homologue. The coenzyme Q homologue distribution is tissue dependent with relatively high coenzyme Q10 content in brain mitochondria, irrespective of the rat strain used. There is no constant relationship of the coenzyme Q content in mitochondria and microsomes fractions. Most organisms tested (including other mammals, bird and fish specimens) have only coenzyme Q10, while the protozoan Tetrahymena pyriformis contains only coenzyme Q8.

Role of vitamin E and phenolic compounds in the antioxidant capacity, measured by ESR, of virgin olive, olive and sunflower oils after frying

Abstract The effect of lipid profile, vitamin E and total phenolic content was studied in relation to the antioxidant capacity (measured by ESR) of three edible oils (virgin olive, sunflower and olive oils), using short-time deep fat frying as a model. Physico-chemical changes in the oils were also studied. Samples were analysed before and after 15, 30, 45 and 60 min fryings. Determination of free radicals, by electron spin resonance spectroscopy, revealed the highest antioxidant capacity in virgin olive oil and sunflower oil. This parameter was mainly influenced by vitamin E content, followed by lipid profile and phenolic content. The frying procedure decreased the antioxidant capacity in all tested oils. Sunflower oil underwent more chemical changes by frying than did olive and virgin olive oils. Antioxidant capacity of the edible oils was correlated with polar components and ultraviolet indices but not with peroxide index or acidity value. The use of ESR, as a rapid and very sensitive method for determining antioxidant capacity of edible oils, is suggested.

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.

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.

Changes in mitochondrial and microsomal rat liver coenzyme Q9 and Q10 content induced by dietary fat and endogenous lipid peroxidation

The influence of different kinds of dietary fat (8%) and of endogenous lipid peroxidation with regard to coenzyme Q9 (CoQ9) and coenzyme Q10 (CoQ10) concentrations in mitochondria and microsomes from rat liver has been investigated by means of an HPLC technique. Although the different diet fats used did not produce any effect on microsomes, it was possible to show that each experimental diet differently influenced the mitochondrial levels of CoQ9 and CoQ10. The highest mitochondrial CoQ content was found in case of a diet supplemented with corn oil. An endogenous oxidative stress induced by adriamycin was able to produce a sharp decrease in mitochondrial CoQ9 levels in the rats to which corn oil was administered. The results suggest that dietary fat ought to be considered when studies concerning CoQ mitochondrial levels are carried out.

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.

Physical exercise affects the lipid profile of mitochondrial membranes in rats fed with virgin olive oil or sunflower oil.

The effects of physical exercise on the lipid profile in mitochondrial membranes of liver and skeletal muscle were examined in rats fed with virgin olive oil or sunflower oil. Thirty male Wistar rats, 21 d old, were randomly assigned to four groups according to fat ingestion and physical activity over an 8-week period. For each type of oil, one group acted as a control group while rats from the other were trained to run for 40 min daily on a horizontal treadmill, at a speed of 35 m/min. The results show that diet affected the fatty acid profile of the mitochondrial membranes from skeletal muscle and liver. Physical exercise also modified the fatty acid profile of the mitochondrial membranes. Total monounsaturated fatty acids decreased (P < 0.001) in liver mitochondria of exercised animals. Total polyunsaturated fatty acids in mitochondrial membranes of liver increased (P < 0.005) after exercise but those in mitochondrial membranes of skeletal muscle decreased (P < 0.05). These changes due to the exercise may arise via several mechanisms, e.g. fluidity regulation; changes in the eicosanoid metabolism; differences in the availability or oxidation rate of the different fatty acids.

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, f -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 f -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.