José Mataix

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.

Fatty acid composition of nuts – implications for cardiovascular health

It is well established that, due to their high content of saturated fatty acids (SFA), the intake of meat and meat products is strongly associated with elevated blood cholesterol concentrations and an increased risk of hypertension, diabetes and cardiovascular diseases. Conversely, the intake of foods rich in unsaturated fatty acids, such as those contained in most vegetable fats and oils and oily fish, is associated with improved lipid profiles, a lower potency of intermediate biomarkers of atherosclerosis and lesser incidence of cardiovascular diseases. There are persuasive evidences that dietary substitution of monounsaturated fatty acids (MUFA) or n-6 polyunsaturated fatty acids (PUFA) for SFA lowers blood cholesterol and may have beneficial effects on inflammation, thrombosis, and vascular reactivity. MUFA may have an advantage over PUFA because enrichment of lipoprotein lipids with MUFA increases their resistance to oxidation. Marine n-3 PUFA have a number of anti-atherosclerotic effects, including anti-arrhythmic properties and, at relatively high doses, reduce serum triglycerides. These effects appear to be shared in part by vegetable n-3 PUFA. Nuts are natural foods rich in unsaturated fatty acids; most nuts contain substantial amounts of MUFA, while walnuts are especially rich in both n-6 and n-3 PUFA. Healthy fats in nuts contribute to the beneficial effects of frequent nut intake observed in epidemiological studies (prevention of coronary heart disease, diabetes, and sudden death) and in short-term feeding trials (cholesterol lowering, LDL resistance to oxidation, and improved endothelial function).

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.

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 concentration and total antioxidant capacity of human milk at different stages of lactation in mothers of preterm and full-term infants

Coenzyme Q10(CoQ10) in human milk at different stages of maturity in mothers of preterm and full-term infants and its relation to the total antioxidant capacity of milk is described for the first time. Thirty healthy breastfeeding women provided colostrum, transition-milk and mature-milk samples. Coenzyme Q, α-, γ- and δ-tocopherol, fatty acids and the total antioxidant capacity of the milk were analyzed. Coenzyme Q10 was found at higher concentrations for colostrum (0.81 ± 0.06 vs. 0.50 ± 0.05 μmol/l) and transition milk (0.75 ± 0.06 vs. 0.45 ± 0.05 μmol/l) in the full-term vs. the preterm group (similar results were found for total antioxidant capacity). Concentrations of α- and γ-tocopherol were higher in the full-term group and decreased with time. In conclusion, CoQ10 is present in breast milk, with higher concentration in mothers of full-term infants. CoQ10 in breast milk decreases through lactation in mothers delivering full-term infants. Also, CoQ10, α- and γ-tocopherol concentration in human milk directly correlates with the antioxidant capacity of the milk.

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.

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.

Olive oil- and fish oil-enriched diets modify plasma lipids and susceptibility of LDL to oxidative modification in free-living male patients with peripheral vascular disease: the Spanish Nutrition Study.

The present study describes a clinical trial in which Spanish patients suffering from peripheral vascular disease (Fontaine stage II) were given specific lipid supplements. Designed as a longitudinal intervention study, patients were provided with olive oil for 3 months, followed by a 3 month wash-out period, then supplemented with a combination of fish oil and olive oil for the final 3 months. Changes in plasma and lipoprotein fatty acid composition and susceptibility of LDL to in vitro oxidation were examined. Furthermore, lipid-supplement-induced changes in LDL properties were measured as relative electrophoretic mobility and macrophage uptake. In addition, thirteen patients not provided with olive oil and fish oil were included as a control group and twenty healthy age-matched individuals were used as a reference group. A complete clinical study and a nutritional survey concerning food habits and lifestyle were performed every 3 months. Yao indices and claudicometry did not change significantly with dietary intervention although changes in plasma lipid composition suggested an improvement in the condition of the patients. The intake of the fish-oil supplement resulted in significantly increased plasma levels of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) in comparison with baseline concentrations, olive-oil and control groups. Fish-oil consumption significantly decreased plasma triacylglycerol levels compared with the olive-oil period, control and reference groups. The susceptibility of LDL to Cu-mediated oxidation was lower in the patients consuming olive oil and the fish-oil supplement than in the control group, and the uptake of LDL by macrophages was significantly lower in the group supplemented with fish oil. In conclusion, consumption of olive oil together with a dietary supplement of fish oil may be useful in the nutritional management of patients suffering from peripheral vascular disease in terms of increasing plasma n-3 long-chain polyunsaturated fatty acids and decreasing susceptibility of LDL to oxidation.

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.