María Dolores Mesa

Oral administration of a turmeric extract inhibits LDL oxidation and has hypocholesterolemic effects in rabbits with experimental atherosclerosis

The oxidation of low-density lipoproteins (LDL) plays an important role in the development of atherosclerosis. Curcumin is a yellow pigment obtained from rhizomes of Curcuma longa and is commonly used as a spice and food colouring. Curcumin and turmeric extracts have several pharmacological effects including antitumour, anti-inflammatory, antioxidant and antiinfectious activities although the precise mechanisms involved remain to be elicited. We evaluated the effect of an ethanol-aqueous extract obtained from rhizomes of C. longa on LDL oxidation susceptibility and plasma lipids in atherosclerotic rabbits. A total of 18 rabbits were fed for 7 weeks on a diet containing 95.7% standard chow, 3% lard and 1. 3% cholesterol, to induce atherosclerosis. The rabbits were divided into groups, two of which were also orally treated with turmeric extract at doses of 1.66 (group A) and 3.2 (group B) mg/kg body weight, respectively. A third group (group C) acted as a control. Plasma and LDL lipid composition, plasma alpha-tocopherol, plasma retinol, LDL TBARS, LDL lipid hydroperoxides and analysis of aortic atherosclerotic lesions were assayed. The low but not the high dosage decreased the susceptibility of LDL to lipid peroxidation. Both doses had lower levels of total plasma cholesterol than the control group. Moreover, the lower dosage had lower levels of cholesterol, phospholipids and triglycerides in LDL than the 3.2-mg dosage. In conclusion, the use of this extract could be useful in the management of cardiovascular disease in which atherosclerosis is important.

Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory biomakers: a systematic review of randomised clinical trials

Inflammation is part of the normal host response to infection and injury. Eicosanoids, cytokines, chemokines, adhesion molecules and other inflammatory molecules are frequently produced during this process. Numerous studies in humans have documented the inflammation-limiting properties of omega-3 fatty acids, but only a few have been randomised clinical trials. The aim of this study was to perform a systematic search of randomised clinical trials on omega-3 fatty acids and inflammatory biomarkers in all subjects including healthy and ill persons up to February 2011 using PubMed and LILACS databases, defined by a specific equation using MeSH terms and limited to randomised clinical trials; there was no any a priori decision to include some diseases and not others. The quality of each publication was validated by using the JADAD scale and the CONSORT checklist. Inflammatory biomarkers were considered as primary outcomes. Twenty-six publications of the last 10 years were selected. Studies included healthy subjects and patients with cardiovascular disease and other chronic and acute diseases; all reported the number of subjects, type of study, type and doses of omega-3 fatty acids, main outcomes and major inflammatory biomarkers. Dietary omega-3 fatty acids are associated with plasma biomarker levels, reflecting lower levels of inflammation and endothelial activation in cardiovascular disease and other chronic and acute diseases, including chronic renal disease, sepsis and acute pancreatitis. However, further research is required before definitive recommendations can be made about the routine use of omega-3 fatty acids in critically ill patients or with neurodegenerative or chronic renal disease.

Sunflower, virgin-olive and fish oils differentially affect the progression of aortic lesions in rabbits with experimental atherosclerosis

In this study we report the effects of sunflower, virgin olive and fish oils on the progression of aortic lesions. A total of 24 male New Zealand rabbits (six per each group) were fed for 50 days on a diet containing 3% lard and 1.3% cholesterol, to induce atherosclerosis. An atherogenic control group (A) was killed after this period and three groups were fed for an additional period of 30 days with a diet composed of (1.75 g of supplemented oil and 98.25 of standard chow): sunflower oil (S), virgin olive oil (O) and fish oil (F). A control group (n=6) was fed with a standard chow diet for 80 days. LDL lipid composition and histological analysis of aortic atherosclerotic lesions were assayed. The atherogenic diet caused a significant increase of cholesterol levels in LDL and aorta tissue. Cholesterol ester content rose significantly in the aortic arch of groups S, O and F. Fatty streaks were found in all aortic sections, although only group S showed a significant progression of the lesion compared with group A. We conclude that the replacement of a high cholesterol-saturated fat diet by another cholesterol free-unsaturated fat diet does not regress atherosclerosis in rabbit. However, sunflower oil provokes a significant progression in lesion development, whereas diet enrichment with extra virgin olive oil and, to a lesser extent, fish oil, stops this progression.

Virgin olive and fish oils enhance the hepatic antioxidant defence system in atherosclerotic rabbits

BACKGROUND & AIMS In this study we report the effects of sunflower, virgin olive and fish oils on the lipid profile and antioxidant defence system in liver mitochondria from rabbits with experimental atherosclerosis. METHOD An atherogenic control group were fed for 50 days on a diet containing 3% lard and 1.3% cholesterol. Four groups were fed for an additional period of 30 days with a diet enriched in different oils: sunflower oil, virgin olive oil, refined olive oil and fish oil. A control group was fed with a standard chow. RESULTS The atherogenic diet caused important changes in the hepatic mitochondria lipid profile and in the enzymatic and non-enzymatic antioxidant defence system accompanied with an increase in the content of hydroperoxides in liver mitochondria. The administration of virgin olive and fish oils showed a better profile in the antioxidant system as well as decrease in the content of hydroperoxides. CONCLUSIONS The intake of cholesterol- and lard-enriched diet leads to a high impairment in the hepatic antioxidant defence system. However, the replacement of that diet by other unsaturated fat-enriched diets using virgin olive, sunflower and fish oil enhances hepatic antioxidant defence system, virgin olive and fish oil diet provide the best results.

Degree of oxidation of low density lipoprotein affects expression of CD36 and PPARγ, but not cytokine production, by human monocyte-macrophages

Oxidized low-density lipoprotein (oxLDL) exhibits many atherogenic effects, including the promotion of monocyte recruitment to the arterial endothelium and the induction of scavenger receptor expression. However, while atherosclerosis involves chronic inflammation within the arterial intima, it is unclear whether oxLDL alone provides a direct inflammatory stimulus for monocyte-macrophages. Furthermore, oxLDL is not a single, well-defined entity, but has structural and physical properties which vary according to the degree of oxidation. We tested the hypothesis that the biological effects of oxLDL will vary according to its degree of oxidation and that some species of oxLDL will have atherogenic properties, while other species may be responsible for its inflammatory activity. The atherogenic and inflammatory properties of LDL oxidized to predetermined degrees (mild, moderate and extensive oxidation) were investigated in a single system using human monocyte-derived macrophages. Expression of CD36 mRNA was up-regulated by mildly- and moderately-oxLDL, but not highly-oxLDL. The expression of the transcription factor, proliferator-activated receptor-gamma (PPARgamma), which has been proposed to positively regulate the expression of CD36, was increased to the greatest degree by highly-oxLDL. However, the DNA binding activity of PPARgamma was increased only by mildly- and moderately-oxLDL. None of the oxLDL species appeared to be pro-inflammatory towards monocytes, either directly or indirectly through mediators derived from lymphocytes, regardless of the degree of oxidation.

Chronic Diarrhea Impairs Intestinal Antioxidant Defense System in Rats at Weaning

The aim of the present study was to evaluate the influence of severe protein–energy malnutrition on the antioxidant defense system in the small and large intestine in rats at weaning. Chronic diarrhea and the subsequent malnutrition were induced by oral intake of a lactose-enriched diet. Twenty rats were weaned at 21 days of age, and the control group was fed a semipurified synthetic diet for two weeks. The malnourished group was fed the same diet but carbohydrates were replaced by lactose, and they developed diarrhea one day after. Rats were killed, and macroscopic and histological features were analyzed, DNA content was measured, and alkaline phosphatase, myeloperoxidase, and γ-glutamyltranspeptidase activities were determined to assess the degree of intestinal injury. Glutathione levels as well as the activities of intestinal glutathione transferase, glutathione reductase, total glutathione peroxidase, selenium-dependent glutathione peroxidase, superoxide dismutase, and catalase were measured to study the antioxidant defense system. Malnourished rats showed loss of body weight and an increase in length and weight in jejunum and ileum, while no significant changes were observed in colon. Epithelial cells showed fewer and shorter microvilli, larger mitochondria with low inner density and loss of cristae, dilated endoplasmic reticulum, and Golgi apparatus. The protein-to-DNA ratio was higher in the jejunum, ileum, and colon of malnourished rats. Glutathione levels decreased 40% in jejunum and 50% in colon of malnourished rats. A 40–50% decrease in the activity of all the enzymes of the antioxidant defense system was observed in the jejunum and ileum of malnourished rats, while only catalase and glutathione transferase activities decreased 50% in colon. These results suggest that early chronic diarrhea and severe protein–energy malnutrition impair the antioxidant defense system in both the small and large intestine, which may have a role in the pathogenesis and maintenance of the vicious circle of malabsorption–diarrhea–malnutrition in infancy.

Influence of an eicosapentaenoic and docosahexaenoic acid-enriched enteral nutrition formula on plasma fatty acid composition and biomarkers of insulin resistance in the elderly

BACKGROUND & AIMS n-3 Polyunsaturated fatty acids may improve cardiovascular outcomes in elderly. The aim of this study was to determine the effect of feeding elderly patients exclusively with an n-3 polyunsaturated fatty acid-enriched diet specifically designed for enteral nutrition for 6 months, evaluating modifications in plasma fatty acid profile and some biomarkers of insulin resistance (IR). METHODS Thirty-two patients >65 years were fed a new enteral formula (T-Diet Plus) containing 75 mg/l of eicosapentaenoic acid (EPA) and 35 mg/l of docosahexaenoic acid (DHA) and 33 were fed an enteral diet intended for elderly (Jevity). Blood samples were drawn at the beginning and after 3 and 6 months of feeding. Plasma lipids, total plasma and lipid fraction fatty acid profiles, and some IR-associated adipokines were analysed. RESULTS Feeding on T-Diet Plus allowed EPA and DHA incorporation into plasma lipids and normalised blood triacylglycerols (TAG) levels after 3 months without major changes in IR, leptin and adiponectin. CONCLUSIONS Feeding the elderly exclusively with an enteral formula enriched with EPA and DHA improves their plasma lipid fatty acid profile and lowers TAG, a well known cardiovascular risk biomarker, without affecting IR.

Plasma Inflammatory and Vascular Homeostasis Biomarkers Increase During Human Pregnancy but Are Not Affected by Oily Fish Intake

The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P < 0.001), whereas plasma matrix metalloproteinase 9, IL-6, TNFα, and nerve growth factor concentrations were not affected. Vascular homeostasis biomarkers soluble E-selectin, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule (sICAM)-1, and total plasminogen activator inhibitor-1 increased as pregnancy progressed (P < 0.001). The plasma sICAM-1 concentration was greater in the control group than in the salmon group at wk 20 (baseline) and 38 (P = 0.007) but there was no group x time interaction, and when baseline concentration was used as a covariate, the groups did not differ (P = 0.69). The remaining biomarkers analyzed were similar in both groups. Therefore, although some inflammatory and vascular homeostasis biomarkers change during pregnancy, they are not affected by the increased intake of farmed salmon.

Vitamin D: Classic and Novel Actions

Background: Classically, vitamin D has been implicated in bone health by promoting calcium absorption in the gut and maintenance of serum calcium and phosphate concentrations, as well as by its action on bone growth and reorganization through the action of osteoblasts and osteoclasts cells. However, in the last 2 decades, novel actions of vitamin D have been discovered. The present report summarizes both classic and novel actions of vitamin D. Summary: 1,25(OH)2 vitamin D, the active metabolite of vitamin D, also known as calcitriol, regulates not only calcium and phosphate homeostasis but also cell proliferation and differentiation, and has a key a role to play in the responses of the immune and nervous systems. Current effects of vitamin D include xenobiotic detoxification, oxidative stress reduction, neuroprotective functions, antimicrobial defense, immunoregulation, anti-inflammatory/anticancer actions, and cardiovascular benefits. The mechanism of action of calcitriol is mediated by the vitamin D receptor, a subfamily of nuclear receptors that act as transcription factors into the target cells after forming a heterodimer with the retinoid X receptor. This kind of receptors has been found in virtually all cell types, which may explain its multiple actions on different tissues. Key Messages: In addition to classic actions related to mineral homeostasis, vitamin D has novel actions in cell proliferation and differentiation, regulation of the innate and adaptative immune systems, preventive effects on cardiovascular and neurodegenerative diseases, and even antiaging effects.

Does Consumption of Two Portions of Salmon Per Week Enhance the Antioxidant Defense System in Pregnant Women

Salmon is a rich source of marine n-3 fatty acids, which may increase oxidative stress and, in turn, could affect the antioxidant defense system in blood plasma and erythrocytes of pregnant women. The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Higher selenium and retinol plasma concentrations were observed after dietary salmon supplementation. Besides, a concomitant increase in selenium and glutathione concentration as well as glutathione peroxidase and reductase activities were detected as pregnancy progressed. However, tocopherols, retinol, β-carotene, and coenzyme Q(10) decreased in late pregnancy. Collectively, our findings lead to the hypothesis that increased farmed salmon intake may increase antioxidant defenses during pregnancy. Clinical trials identifier NCT00801502.