Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition.

An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular ß-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources.

Impact of diet on breast cancer risk: a review of experimental and observational studies.

Breast cancer, which presents the highest global incidence of all female cancers, is caused by the interaction of genetic and environmental factors. Among the latter, diet has attracted considerable attention, as it is a modifiable risk factor and thus offers an opportunity to design preventive strategies. Nevertheless, only alcohol consumption has been unequivocally related to increased breast cancer risk. Despite the failure of observational studies in human populations to clearly define the nature of the relationship between specific nutrient exposures and breast cancer risk, in vivo and in vitro studies strongly suggest its existence. Moreover, studies at the molecular level have identified the putative action mechanism by which the nutritional constituents of specific foodstuffs may exert protective or enhancing effects with respect to breast cancer risk. The inadequate experimental design of some observational studies, or the occurrence of measurement errors and/or recall bias during data collection, or insufficient follow-up and subject characterization, may underlie these controversies. By improving the methods used to study the relationship between diet and breast cancer risk, and by applying new technologies linked to novel approaches such as "nutrigenomics," it might be possible to derive effective recommendations for breast cancer prevention and thus improve anti-cancer treatment.

Effects of fish oil supplementation on the fatty acid profile in erythrocyte membrane and plasma phospholipids of pregnant women and their offspring: a randomised controlled trial.

We aimed to investigate the effects of fish oil (FO) supplementation to pregnant women on the maternal and fetal fatty acid profile in plasma and erythrocyte phospholipids (PL) and to identify the best compartment for the assessment of fatty acid status. A multi-centre, double-blind, controlled trial was conducted. Healthy pregnant women from three European centres were randomly assigned to receive from week 20 of gestation until delivery a daily dietary supplement with either FO (500 mg DHA+150 mg EPA), 400 µg 5-methyltetrahydrofolate, both or placebo. Fatty acids in plasma and erythrocyte PL were determined in maternal blood (week 20, week 30 of pregnancy and delivery) and in cord blood (delivery). FO supplementation increased DHA levels in maternal and cord plasma and erythrocyte PL. Higher percentage changes were observed in erythrocyte PL than in plasma PL. There were significant correlations between plasma and erythrocyte fatty acid levels in maternal and cord blood. Significant correlations between maternal and cord fatty acid levels at delivery in plasma and erythrocytes were also observed; however, correlation coefficients were higher for erythrocyte phophatidylethanolamine. FO supplementation increases maternal and fetal DHA status. Both plasma and erythrocytes appear to be suitable to evaluate the fatty acid status of mothers but erythrocytes seem to be a more reliable marker in neonates.

Oxidative stress status in liver mitochondria and lymphocyte DNA damage of atherosclerotic rabbits supplemented with water soluble coenzyme Q10.

The effects of the administration of water soluble coenzyme Q10 (25 mg/kg per day) over 30 days, after 50 days feeding on a high-fat diet (3% lard + 1.3% cholesterol), were investigated in the plasma and liver mitochondria of rabbits. Results showed that this atherogenic diet enhanced lipid levels both in plasma and liver mitochondria, reduced plasma and mitochondrial concentrations of retinol and coenzyme Q10, led to higher DNA damage in peripheral blood lymphocytes and reactive oxygen species concentration in liver mitochondria. The treatment of animals with coenzyme Q10 reduced (to the healthy group levels) lipid concentration in liver mitochondria with no effect on plasma lipids, increased mitochondrial levels of alpha-tocopherol, restored mitochondrial coenzyme Q10 and improved alpha-tocopherol levels in plasma. Moreover, coenzyme Q10 supplementation reduced mitochondrial reactive oxygen species levels and decreased DNA damage in peripheral blood lymphocytes. The findings suggest that antioxidant therapy with coenzyme Q10 may be used in the treatment of liver pathologies associated to the intake of high-fat, atherogenic, diets.

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.

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, alpha-, gamma- and delta-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 micromol/l) and transition milk (0.75+/-0.06 vs. 0.45+/-0.05 micromol/l) in the full-term vs. the preterm group (similar results were found for total antioxidant capacity). Concentrations of alpha- and gamma-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, alpha- and gamma-tocopherol concentration in human milk directly correlates with the antioxidant capacity of the milk.

Coenzyme Q Protects Against Age-Related Alveolar Bone Loss Associated to n-6 Polyunsaturated Fatty Acid Rich-Diets by Modulating Mitochondrial Mechanisms.

An age-dependent model of the periodontium was reproduced to evaluate the effect of life-long feeding on a low coenzyme Q10 dosage in n-6, n-3 polyunsaturated fatty acid or monounsaturated fatty acid-based diets on periodontal tissues of young and old rats. Results shown that exacerbated age-related alveolar bone loss previously associated to n-6 polyunsaturated fatty acid diet was attenuated by coenzyme Q10 Gene expression analysis suggests that involved mechanisms might be related to a restored capacity of mitochondria to adapt to aging in gingival cells from rats fed on n-6 polyunsaturated fatty acid. In particular, this could be due to an age-related increase of the rate of mitochondrial biogenesis and a better oxidative and respiratory balance in these animals. From the nutritional and clinical point of view, it is noteworthy that supplementation with coenzyme Q10 could counteract the negative effects of n-6 polyunsaturated fatty acid on alveolar bone loss (a major feature of periodontitis) associated to age.

Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits.

OBJECTIVE: This study evaluates the effect of a Curcuma longa extract on the development of experimental atherosclerosis (fatty streak) in rabbits and its interaction with other plasmatic antioxidants. METHODS AND RESULTS: Two experimental groups of male New Zealand White rabbits, a control group and a curcuma-extract (CU) group, were fed an atherogenic diet. Additionally, the CU group received an oral curcuma hydroalcoholic extract. Six animals from each experimental group were killed after 10, 20, and 30 days. Compared with the CU group, the control group showed significantly higher plasma lipid peroxide at all experimental times (10, 20, and 30 days) and significantly lower alpha-tocopherol and coenzyme Q levels at 20 and 30 days. Histological results for the fatty streak lesions revealed damage in the thoracic and abdominal aorta that was significantly lower in the CU group than in the control group at 30 days. CONCLUSIONS: Supplementation with Curcuma longa reduces oxidative stress and attenuates the development of fatty streaks in rabbits fed a high cholesterol diet.

Monounsaturated and omega-3 but not omega-6 polyunsaturated fatty acids improve hepatic fibrosis in hypercholesterolemic rabbits.

OBJECTIVE: Although the influence of saturated fatty acids, monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), lipids, cholesterol levels, and other blood lipids has been established, few studies have examined the influence of these dietary lipids on the composition and histologic damage of organs in situations of hypercholesterolemia. Biliary lipids come from the liver, and this organ is essential in cholesterol homeostasis; thus, it may be helpful to evaluate the inter-relations among biliary, hepatic lipids, and hepatotoxic effects in situations of hypercholesterolemia with different dietary lipids. This study investigated whether administration of diets differing in fatty acid profiles (omega-3 PUFA, omega-6 PUFA, or MUFA) influence the content of biliary lipids, the lithogenic index of gallbladder bile, and the development of hepatic fibrosis in hypercholesterolemic rabbits. METHODS: Thirty rabbits were randomized to one of five groups. A control group received rabbit chow for 80 d. The remaining four groups received a 50-d diet that contained 3% lard and 13% cholesterol to provoke hypercholesterolemia. After this period, three groups were fed for another 30 d on a diet enriched with omega-6 PUFAs, MUFAs, and omega-3 PUFAs, respectively. Liver, bile, and plasma lipid compositions, lipid peroxidation in hepatic mitochondria, and histologic hepatic lesions were analyzed. RESULTS AND CONCLUSIONS: There was a beneficial effect of MUFA and omega-3 PUFA on hepatic fibrosis in hypercholesterolemic rabbits because both dietary fats led to recovery from hepatic lesions. However, because intake of omega-3 PUFA provoked lithogenic bile in rabbits, MUFA intake would be more advisable.

[Experimental evidence on the role of different types unsaturated fats in the diet on ageing]. / Evidencias experimentales con respecto al papel de distintos tipos de grasas insaturadas de la dieta en el envejecimiento.

Nutrition has been largely related to the physiological ageing process. Several nutrients, such as certain types of dietary fat and various antioxidants have been shown to have positive effects on age-related diseases. The type of dietary fat affects mitochondrial structure and function, as well as its susceptibility to oxidative stress, all factors involved in ageing. The present review aims to summarise the studies conducted by our research group in the past 10 years, using virgin olive oil, sunflower oil, or fish oil as a source of unsaturated fat diet relative to a rat model of ageing.

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.

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.

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.

Oral administration of a turmeric extract inhibits erythrocyte and liver microsome membrane oxidation in rabbits fed with an atherogenic diet.

OBJECTIVES: The aim of this study was to evaluate the effects of an oral supplementation with a Curcuma longa ethanol and aqueous extract on the susceptibility to oxidation of cellular and subcellular membranes affected in the atherosclerotic process, such as erythrocyte membranes and liver microsomes, in rabbits fed with a high-fat diet. METHODS: Twenty-four male rabbits were randomly assigned to one of two groups: group T was treated with a turmeric hydroalcoholic extract (1.66 mg/kg of body weight) dissolved in a hydroalcoholic mixture vehicle (7:2), and group C (control): received a curcuma-free hydroalcoholic solution (7:2). All rabbits had access ad libitum to 150 g/d of an experimental diet rich in cholesterol and lard to provoke an atherosclerotic process. Erythrocyte membranes and liver microsomes were isolated, and the levels of hydroperoxides and thiobarbituric acid-reactive substances were measured after oxidation induction. RESULTS: The oxidation of erythrocyte membranes in group T was significantly lower than that in group C, mainly by 30 d (P < 0.05). Levels of hydroperoxides and thiobarbituric acid-reactive substances in liver microsomes also were significantly lower in group T than in group C (P < 0.05). CONCLUSIONS: The results of this study indicated that oral administration of a nutritional dose of C. longa extracts reduces the susceptibility to oxidation of erythrocyte and liver microsome membranes in vitro and may contribute to the prevention of effects caused by a diet high in fat and cholesterol in blood and liver during the development of atherosclerosis.

Comparative analysis of pancreatic changes in aged rats fed life long with sunflower, fish, or olive oils.

An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. We aimed to study the effect of oil consumption on pancreas histology in order to find aging-related signs. To this end, three groups of rats were fed an isocaloric diet for 2 years, where virgin olive, sunflower, or fish oil was included. Pancreatic samples for microscopy and blood samples were collected at the moment of sacrifice. As a result, the sunflower oil-fed rats presented higher ß-cell numbers and twice the insulin content than virgin olive oil-fed animals. In addition, rats fed with fish oil developed acinar fibrosis and macrophage infiltrates in peri-insular regions, compared with counterparts fed with virgin olive oil. Inflammation signs were less prominent in the sunflower group. The obtained data emphasize the importance of dietary fatty acids in determining pancreatic structure.

Oxidative stress status in metastatic breast cancer patients receiving palliative chemotherapy and its impact on survival rates.

Antineoplastic agents are known to induce the production of free radicals leading to cell damage. These adverse effects may fuel the acquisition of new mutations and the development of treatment resistances. We selected 30 metastatic breast cancer patients receiving palliative chemotherapy, and paired blood samples, before and after chemotherapy, were extracted. We analysed DNA, lipid and protein oxidative damage markers and determined the extent of antioxidant and repair defences activation at the systemic level. We found that the DNA repair activity of the KU86 enzyme was significantly lower after chemotherapy and the antioxidant capacity of the plasma was significantly higher after treatment. Cox regression analysis revealed a significant effect of KU86 activity on the survival rates of those patients who received anthracyclines as part of their treatment. The high clinical heterogeneity of metastatic breast cancer patients warrants further studies to clarify the role of DNA repair and systemic antioxidant capacities during chemotherapy.

Squalene ameliorates atherosclerotic lesions through the reduction of CD36 scavenger receptor expression in macrophages.

SCOPE: Anti-atherogenic features of olive oil (OO) have been attributed, in part, to minor compounds, via diverse mechanisms, although its effects on the CD36 receptor have not been examined. We investigated the effects of minor compounds of OO (squalene (SQ), tyrosol (Tyr) and hydroxytyrosol (OH-Tyr)), on the expression of the CD36 receptor, as well as on monocyte/macrophage differentiation and proliferation. METHODS AND RESULTS: U937 monocytic cells and macrophages (obtained with 10 nM phorbol-myristate-acetate) were exposed to Tyr, OH-Tyr or SQ at 0, 10, 75 and 200 µM with/without native or oxidised LDL(oxLDL). Flow cytometry was used to achieve the expression of CD36 in both cell types exposed to oxLDL plus antioxidants, as well as the inhibition of monocyte/macrophage differentiation after oxLDL and apoptosis. SQ caused a dose-dependent reduction of CD36 in the presence of native and moderate LDL in monocytes and macrophages. Phenotype-dependent cytotoxic and antiproliferative effects were found for OH-Tyr (p < 0.05), while SQ affected neither monocytes nor macrophages (p < 0.01). CONCLUSION: SQ does not prevent monocyte migration and activation into macrophages, but it would inhibit oxLDL uptake by macrophages, by reducing CD36 expression. This study provides new data about the role of the components of OO in the prevention of atherosclerosis.

Free radicals in breast carcinogenesis, breast cancer progression and cancer stem cells. Biological bases to develop oxidative-based therapies.

Oxidative stress leads to lipid, carbohydrate, protein and DNA damage in biological systems and affects cell structure and function. Breast cancer cells are subjected to a high level of oxidative stress, both intracellular and extracellular. To survive, cancer cells must acquire adaptive mechanisms that counteract the toxic effects of free radicals exposure. These mechanisms may involve the activation of redox-sensitive transcription factors, increased expression of antioxidant enzymes and antiapoptotic proteins. Moreover, recent data maintain that different breast cancer cell types, show different intracellular antioxidant capacities that may determine their ability to resist radio and chemotherapy. The resistant cell type has been shown to correspond with tumor initiating cells, also known as cancer stem cells (CSCs), which are thought to be responsible for tumor initiation and metastasis. Abrogation of the above-mentioned adaptive mechanisms by redox regulation in cancer cells opens a promising research line that could have significant therapeutic applications.

Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours.

SCOPE: Hydroxytyrosol (a phenolic compound derived from virgin olive oil) has demonstrated an anti-tumour effect in several tumour cell lines in addition to other health-related properties. The aim of this study was to investigate, for the first time in an animal model of experimental mammary carcinoma, the anti-cancer ability of hydroxytyrosol and to discover which pathways are modified by hydroxytyrosol. METHODS AND RESULTS: Dimethylbenz[α]anthracene-induced mammary tumours were induced in 28 female Sprague-Dawley rats and ten of them were treated with hydroxytyrosol (0.5 mg/kg b.w. 5 days/week for 6 wk). cDNA microarray and quantitative RT-PCR experiments were performed. Hydroxytyrosol was found to inhibit the experimental mammary tumour growth and proliferation rate, with results comparable to those of doxorubicin but better with regard to the histopathological outcome. It also altered the expression of genes related to apoptosis, cell cycle, proliferation, differentiation, survival and transformation pathways. CONCLUSIONS: This study shows that hydroxytyrosol exerts anti-cancer effects in Sprague-Dawley rats with experimental mammary tumours, inhibiting growth and cell proliferation in mammary tumours. Moreover, hydroxytyrosol alters several genes associated with cell proliferation, apoptosis and the Wnt signalling pathway, promoting a high expression of Sfrp4. However, further studies are necessary to better understand the mechanisms of hydroxytyrosol.

Does chemotherapy-induced oxidative stress improve the survival rates of breast cancer patients?

Antineoplastic agents induce oxidative stress leading to lipid, carbohydrate, protein, and DNA damage. We sought to explore the role of drug-induced oxidative stress on breast cancer patient's survival. We observed that neoadjuvant patients presented a marked raise in DNA damage and protein carbonyl levels after chemotherapy, whereas postchemotherapy DNA repair activity of the KU86 enzyme and total antioxidant capacity of the plasma were higher in the adjuvant group. With respect to patient's survival, we observed that increasing levels of KU86 and antioxidant capacity of the plasma during chemotherapy significantly influenced the survival rates of the patients, protecting from disease recurrence and death. Our results suggest that chemotherapy induces a certain level of systemic oxidative stress, which is maintained along successive clinical interventions and could influence the clinical outcome of the patients.