Pomace Olive Oil Concentrated in Triterpenic Acids Restores Vascular Function, Glucose Tolerance and Obesity Progression in Mice.

Pomace olive oil, an olive oil sub-product, is a promising source of bioactive triterpenoids such as oleanolic acid and maslinic acid. Considering the vascular actions of pomace olive oil and the potential effects of the isolated oleanolic acid on metabolic complications of obesity, this study investigates for the first time the dietary intervention with a pomace olive oil with high concentrations of the triterpenic acids (POCTA), oleanolic and maslinic acid, during diet-induced obesity in mice. The results demonstrate that obese mice, when switched to a POCTA-diet for 10 weeks, show a substantial reduction of body weight, insulin resistance, adipose tissue inflammation, and particularly, improvement of vascular function despite high caloric intake. This study reveals the potential of a functional food based on pomace olive oil and its triterpenic fraction against obesity progression. Our data also contribute to understanding the health-promoting effects attributable to the Mediterranean diet.

Rice bran prevents high-fat diet-induced inflammation and macrophage content in adipose tissue.

BACKGROUND: The inflammatory process associated with obesity mainly arises from white adipose tissue (WAT) alterations. In the last few years, nutritional-based strategies have been positioned as promising alternatives to pharmacological approaches against these pathologies. Our aim was to determine the potential of a rice bran enzymatic extract (RBEE)-supplemented diet in the prevention of metabolic, biochemical and functional adipose tissue and macrophage changes associated with a diet-induced obesity (DIO) in mice. METHODS: C57BL/6J mice were fed high-fat diet (HF), 1 and 5 % RBEE-supplemented high-fat diet (HF1 % and HF5 %, respectively) and standard diet as control. Serum cardiometabolic parameters, adipocytes size and mRNA expression of pro-inflammatory biomarkers and macrophage polarization-related genes from WAT and liver were evaluated. RESULTS: RBEE administration significantly decreased insulin resistance in obese mice. Serum triglycerides, total cholesterol, glucose, insulin, adiponectin and nitrites from treated mice were partially restored, mainly by 1 % RBEE-enriched diet. The incremented adipocytes size observed in HF group was reduced by RBEE treatment, being 1 % more effective than 5 % RBEE. Pro-inflammatory biomarkers in WAT such as IL-6 and IL-1ß were significantly decreased in RBEE-treated mice. Adiponectin, PPARγ, TNF-α, Emr1 or M1/M2 levels were significantly restored in WAT from HF1 % compared to HF mice. CONCLUSIONS: RBEE-supplemented diet attenuated insulin resistance, dyslipidemia and morphological and functional alterations of adipose tissue in DIO mice. These benefits were accompanied by a modulating effect in adipocytes secretion and some biomarkers associated with macrophage polarization. Therefore, RBEE may be considered an alternative nutritional complement over metabolic syndrome and its complications.

Structural, mechanical and myogenic properties of small mesenteric arteries from ApoE KO mice: characterization and effects of virgin olive oil diets.

OBJECTIVE: We analyzed the structural, mechanical, myogenic and functional properties of resistance arteries of ApoE KO compared to wild type (WT) mice. We also determined the influence of saturated fat in comparison to virgin olive oil-enriched diets in vascular wall abnormalities. METHODS: Male ApoE KO (ApoE) and WT mice (8-weeks-old) were assigned to the groups: standard chow diet (SD), high fat diet (HFD), virgin olive oil (VOO) and high polyphenol-VOO-enriched diet (Oleaster(®)) (OT) (15% w/w). After 20 weeks, structural, mechanical and myogenic properties of isolated small mesenteric arteries (SMA) were analyzed by pressure myography. For functional studies, vasodilatation to acetylcholine was assessed. Arterial superoxide anion production was measured by ethidium fluorescence. RESULTS: Hypertrophic remodeling and distensibility in ApoE KO SMA was lower compared to WT mice, suggesting an alteration in the autoregulation mechanisms aimed to compensate disease progression. However, ApoE deficiency resulted in a lower impairment in myogenic tone in response to intraluminal pressure, in addition to an improved endothelium-dependent hyperpolarizing vasodilatation. Also, we evidenced the beneficial effects of VOO in contrast to a saturated fat-enriched diet on SMA wall disorders. Only the endothelial function improvement induced by olive oil was dependent on polyphenols content. CONCLUSION: Resistance arteries structure, mechanic, myogenic and functional responses from ApoE KO mice significantly differ from WT mice, evidencing the influence of the type of diet on these disorders. These results are particularly useful to determine the contribution of resistance arteries during the atherosclerotic process and to provide novel insights into the Mediterranean dietary pattern to reduce the burden of atherosclerotic disease.

Rice bran enzymatic extract-supplemented diets modulate adipose tissue inflammation markers in Zucker rats.

OBJECTIVE: Chronic low-grade inflammation in obesity is characterized by macrophage accumulation in white adipose tissue and adipokine production deregulation. Obesity also is characterized by oxidative stress related to inflammatory signaling. The aim of this study was to analyze whether dietary supplementation with a rice bran enzymatic extract (RBEE), rich in bioactive compounds with antioxidant and hypocholesterolemic properties, would ameliorate the inflammatory state existing in visceral adipose tissue of obese Zucker rats. METHODS: Obese Zucker rats and their littermate controls, lean Zucker rats ages 8 wk, were daily fed an enriched diet with either 1% or 5% RBEE supplementation over 20 wk. Measurement of adipocyte size and mRNA expression of proinflammatory molecules from visceral abdominal/epididymal tissue was performed. RESULTS: An RBEE-supplemented diet decreased the overproduction of tumor necrosis factor-α, interleukin (IL)-6, IL-1 ß, and inducible nitric oxide synthase (iNOS), as well as the overproduction of IL-6 and iNOs in visceral abdominal adipose tissue and visceral epididymal adipose tissue, respectively. An RBEE-supplemented diet modified the adipocyte-size distribution pattern in both abdominal and epididymal adipose tissue, shifting it toward smaller cell sizes. CONCLUSIONS: Chronic administration of a novel water-soluble RBEE, rich in polyphenols, tocotrienols and γ-oryzanol, could be a suitable treatment to ameliorate the obesity-associated proinflammatory response.

Influence of pharmaceutical care on the delayed emesis associated with chemotherapy.

BACKGROUND: Complete control of emesis during chemotherapy remains to be achieved. This could be improved by increasing adherence to medicines and recommendations. OBJECTIVE: The aim of this study was to analyse the effects of pharmaceutical care on the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) in adult cancer outpatients. METHOD: This is a longitudinal prospective intervention study. Patients included were those who received a new cancer intravenous treatment. We compared complete response (no vomiting and no rescue treatment) and the incidence of nausea in the control group (CG) and in the intervention group (IG), as well as patients' adherence. Pharmaceutical intervention consisted of: reviewing the antiemetic protocol and giving some recommendations to the patients. RESULTS: 102 patients were studied. In the delayed phase complete response was achieved in 84.8 % of the patients in the IG, compared with 69.6 % in the control group [absolute risk reduction (ARR), 15.2 %; p = 0.144]. Regarding absence of vomiting, the difference was higher (71.0 CG vs 97.0 % IG, ARR, 26.0%; p = 0.002). Absence of delayed nausea were also better in the IG (61 vs. 52 %). Compliant patients increased from 59 to 76 %. CONCLUSION: The intervention of a pharmacist reduced the incidence of delayed CINV and improved medication adherence.

Women as whole blood donors: offers, donations and deferrals in the province of Huelva, south-western Spain.

BACKGROUND: Women seem more willing to donate blood than men despite the limitations that affect their donation rate. The aim of our study was to determine the role of women in altruistic donation of blood in Huelva, a province in south-western Spain. MATERIALS AND METHODS: We registered 87,601 offers to donate whole blood between January 1st, 2005 and December 31st, 2009. We statistically analysed variables such as sex, age, offers, deferrals and donations, problems in venous access, vasovagal reactions, weight and blood pressure to establish their significance according to donor gender. RESULTS: With regards to gender, 52.3% of donors were women and 47.7% men. Of the 87,601 offers to donate blood, 46.5% were from females and 53.5% from males. More females than males made their first donation during the study period. However, 43.9 % of donations were from women, whereas 56.1% were from men. Overall 8.7% of offers were deferred, 62.7% of which due to a low haemoglobin concentration, which was the most frequent cause of deferral in women. Difficulties in venous access and vasovagal reactions were also more frequent in female donors than in male donors. By the end of the study period, donor fidelity was 58.6% for men and 48.6% for women. DISCUSSION: In the province of Huelva, women are more altruistically inclined than men to give blood, with the percentages of donors and first-time donors being higher among females. However, there are restrictions to women giving blood, especially low haemoglobin concentration, which reduce the number of female blood donations. Women also have more difficulty when blood is withdrawn and are more susceptible to vasovagal reactions, which negatively affect their experience as donors. Measures should be taken to reduce these barriers to encourage women to continue to offer to donate blood, thereby ensuring that they become regular donors, which is a key factor in guaranteeing an adequate supply of blood within the region of Andalusia.

Rice bran enzymatic extract restores endothelial function and vascular contractility in obese rats by reducing vascular inflammation and oxidative stress.

BACKGROUND: Rice bran enzymatic extract (RBEE) used in this study has shown beneficial activities against dyslipidemia, hyperinsulinemia and hypertension. Our aim was to investigate the effects of a diet supplemented with RBEE in vascular impairment developed in obese Zucker rats and to evaluate the main mechanisms mediating this action. METHODS AND RESULTS: Obese Zucker rats were fed a 1% and 5% RBEE-supplemented diet (O1% and O5%). Obese and their lean littermates fed a standard diet were used as controls (OC and LC, respectively). Vascular function was evaluated in aortic rings in organ baths. The role of nitric oxide (NO) was investigated by using NO synthase (NOS) inhibitors. Aortic expression of endothelial NOS (eNOS), inducible NOS (iNOS), tumor necrosis factor (TNF)-α and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and superoxide production in arterial wall were determined. Endothelial dysfunction and vascular hyperreactivity to phenylephrine in obese rats were ameliorated by RBEE treatment, particularly with 1% RBEE. Up-regulation of eNOS protein expression in RBEE-treated aortas should contribute to this activity. RBEE attenuated vascular inflammation by reducing aortic iNOS and TNF-α expression. Aortas from RBEE-treated groups showed a significant decrease of superoxide production and down-regulation of NADPH oxidase subunits. CONCLUSION: RBEE treatment restored endothelial function and vascular contractility in obese Zucker rats through a reduction of vascular inflammation and oxidative stress. These results show the nutraceutical potential of RBEE to prevent obesity-related vascular complications.

Endothelium-dependent vasodilator and antioxidant properties of a novel enzymatic extract of grape pomace from wine industrial waste.

The aim of the present study was to evaluate the vascular effects of an enzymatic extract of grape pomace (GP-EE) on isolated arteries, focusing our attention on endothelium-derived relaxation and on its antioxidant properties. Grape pomace derived from wine making was extracted by an enzymatic process and its composition of polyphenols was evaluated by HPLC and ESI-MS/MS, detecting kaempferol, catechin, quercetin and procyanidins B1 and B2, trace levels of resveratrol and tracing out gallocatechin and anthocyanidins. GP-EE induced endothelium- and NO-dependent vasodilatation of both rat aorta and small mesenteric artery (SMA) segments and reduced Phe-induced response in aortic rings. Both ORAC and DPPH assays confirmed antioxidant scavenging properties of GP-EE, which also prevented O(2)(·-) production (assessed by DHE fluorescence) and contraction elicited by ET-1. These results provide evidence that GP-EE possesses interesting antioxidant and protective vascular properties and highlight the potential interest of this extract as a functional food.

Pharmacological effects and clinical applications of propionyl-L-carnitine.

Propionyl-L-carnitine (PLC) is a naturally occurring derivative of carnitine that plays an important role in the metabolism of both carbohydrates and lipids, leading to an increase of ATP generation. PLC, however, is not only a metabolic drug; it is also a potent antiradical agent and thus may protect tissues from oxidative damage. PLC has been demonstrated to exert a protective effect in different models of both cardiac and endothelial dysfunction, to prevent the progression of atherosclerosis, and, more recently, to improve some of the cardiometabolic alterations that frequently accompany insulin resistance. As a result, most of the clinical trials conducted in humans highlight PLC as a potential treatment option in cardiovascular diseases such as peripheral arterial disease, chronic heart failure, or stable angina, especially when type 2 diabetes mellitus or hyperglycemia (i.e., patients on hemodialysis) are also present. The aim of this review is to summarize the pharmacological effects and possible therapeutic applications of PLC, including the most recent findings to date.

Chronic treatment with the cannabinoid 1 antagonist rimonabant altered vasoactive cyclo-oxygenase-derived products on arteries from obese Zucker rats.

To investigate the effect of chronic cannabinoid 1 antagonism on vascular prostanoid production, obese Zucker rats were treated with rimonabant (10 mg/kg per day) during 20 weeks and then vascular and endothelial reactivity were assessed in aortic rings by analyzing response to phenylephrine and acetylcholine. The presence of cyclo-oxygenase-1 and cyclo-oxygenase-2 selective inhibitors (SC-560 and NS-398, respectively) and the enzyme immunoassay revealed lower PGI2 production by aortic rings from obese rats with rimonabant able to restore such response toward levels found in the lean animals. The treatment also reduced TXB2 but did not alter its participation on acetylcholine-induced relaxation as the TP receptor antagonist ICI-192,605 revealed. Those effects were associated with an enhancement of cyclo-oxygenase-2 expression without affecting p38MAPK phosphorylation. Obese rats also exhibited higher nitric oxide plasma concentrations and greater inducible nitric oxide synthase participation on vascular phenylephrine-induced response without changes in inducible nitric oxide synthase protein expression. Although rimonabant reduced such alteration, the values were still higher than those found in lean rats. Finally, rimonabant was also able to reduce tumor necrosis factor-α produced by adipose tissue of obese Zucker rats. These results highlight a crosstalk among cannabinoids and cyclo-oxygenase-derived products in the vasculature of obese animals.

Effects of pomace olive oil-enriched diets on endothelial function of small mesenteric arteries from spontaneously hypertensive rats.

Pomace olive oil (POM), an olive oil subproduct traditionally used in Spain, is a good source of minor components from the unsaponifiable fraction such as triterpenoids, mainly in the form of oleanolic acid, which induces vascular protection and vasodilatation. Our aim was to evaluate the effects of long-term intake of diets enriched in POM with high concentration in oleanolic acid on endothelial dysfunction associated to hypertension in small mesenteric arteries (SMA) from spontaneously hypertensive rats (SHR). During 12 weeks, rats (six rats per group) were fed either a control 2 % maize oil diet (BD), or high-fat diets containing 15 % refined olive oil (OL), pomace olive oil (POM), or pomace olive oil supplemented in oleanolic acid (POMO; up to 800 parts per million). Endothelial and vascular functions were assessed by relaxing or contracting responses to acetylcholine (ACh) or phenylephrine, respectively. The involvement of endothelium-derived relaxing factors in these responses was evaluated. In contrast to BD, SHR fed high-fat diets showed a biphasic response to ACh related to changes in eicosanoid metabolism. POM enhanced the endothelial function in SMA from SHR by increasing the endothelium-derived hyperpolarising factor (EDHF)-type component, whereas administration of POMO resulted in a similar contribution of NO/EDHF in the endothelial response to ACh. The present study shows that despite the lack of changes in blood pressure, consumption of POM improves endothelial function in SMA from SHR by improving the agonist-mediated EDHF/NO response. Thus, triterpenoids confer a protective role to POM against endothelial dysfunction in hypertension.

Pomace olive oil improves endothelial function in spontaneously hypertensive rats by increasing endothelial nitric oxide synthase expression.

BACKGROUND: The effect of dietary pomace olive oil, which has the same concentration of oleic acid but a higher proportion of oleanolic acid (OA) than olive oil, was examined on animal models of hypertension for the first time. METHODS: During 12 weeks, Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were fed with either a control 2% corn oil diet (BD), or high-fat diets containing 15% of refined olive oil (OL), pomace olive oil (POM), or pomace olive oil supplemented in OA (up to 800 ppm) (POMO). Then, vascular reactivity and endothelial nitric oxide (NO) synthase (eNOS) expression were studied in aortic rings. Plasma nitrite + nitrate levels were also determined. RESULTS: Diets had no effects on blood pressure (BP). In contrast to the BD and OL dietary groups, POM intake improved relaxation evoked by acetylcholine in SHR aorta. The POMO intake increased vasodilatation to acetylcholine and attenuated phenylephrine-induced contractions in both strains of rats associated with a major NO participation revealed by inhibition of NOS. The enhanced relaxation shown in POM and POMO SHR aorta was attributed to an increased eNOS protein expression. Plasma nitrite levels were also increased in these groups. Although olive and pomace oils used in diets contained similar fatty acid composition, beneficial effects on endothelial function were absent in the OL group. Therefore, these effects must be associated with some minor components from pomace olive oil such as OA. CONCLUSIONS: Chronic intake of diets rich in pomace olive oil improves endothelial dysfunction in SHR aorta by mechanisms associated with enhanced eNOS expression. Important evidence is provided regarding the effects of pomace olive oil and OA on endothelial function in hypertensive animals.

Argan (Argania spinosa) oil lowers blood pressure and improves endothelial dysfunction in spontaneously hypertensive rats.

Traditionally hand-pressed argan oil, obtained from Argania spinosa seeds, is eaten raw in south-west Morocco; its rich composition of tocopherols, MUFA and PUFA make a study of its actions on risk factors for CVD, such as hypertension, interesting. The effects of 7 weeks of treatment with argan oil (10 ml/kg) on the blood pressure and endothelial function of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats were investigated. Systolic blood pressure and heart rate were measured every week by the tail-cuff method and endothelial function was assessed by carbachol (10(-8) to 10(-4) M)-induced relaxations of aortic rings and small mesenteric arteries pre-contracted with phenylephrine. Argan-oil administration reduced the mean blood pressure of SHR after the fifth week of treatment (P<0.05) and increased (P<0.01) the endothelial responses of arteries from SHR. The NO synthase inhibitor, L-N-omega-nitroarginine (3 x 10(-5) M) revealed a greater participation of NO in the relaxant effect after the treatment. When cyclooxygenase (COX) was blocked with indomethacin (10(-5) M), an involvement of COX products in the endothelium-dependent response was characterized. Enzyme immunoassay of thromboxane B2 showed a significant decrease (P<0.05) in the release of thromboxane A2 in both aorta and small mesenteric artery after argan-oil treatment of SHR. Experiments in the presence of the thromboxane A2-prostaglandin H2 receptor antagonist ICI 192,605 (10(-5) M) confirmed this result. Results after incubation with the antioxidants superoxide dismutase and catalase suggested that a decreased oxidative stress might contribute to explain the beneficial effects of argan-oil treatment.

Potential vasorelaxant effects of oleanolic acid and erythrodiol, two triterpenoids contained in 'orujo' olive oil, on rat aorta.

'Orujo' olive oil is obtained by chemical processes from the waste resulting from the mechanical extraction of virgin olive oil. The aim of the present study was to evaluate a new pharmacological property of two natural triterpenoids contained in olive oil, as vasodilatory agents, and to determine their mechanism of action. The two compounds studied were oleanolic acid and erythrodiol. The vasorelaxant effect induced by these pentacyclic triterpenoids was studied in isolated thoracic rat aorta. Oleanolic acid and erythrodiol, accumulatively added, showed vasorelaxant activities in aortic rings with endothelium pre-contracted by 10(-6) m-phenylephrine (maximum percentage of relaxation 86.38 (sem 2.89) and 73.53 (sem 6.01), respectively). They had almost no relaxant effect on depolarised or endothelium-denuded aortic segments. The relaxation was significantly attenuated by pre-treatment with the NO synthase inhibitor N(omega)-nitro-L-arginine-methylester (L-NAME; 3x10(-4) m). To characterise the involvement of endothelial factors, in addition to NO, arteries with endothelium were exposed to 10(-5) m-indomethacin (INDO), a cyclo-oxygenase inhibitor, or INDO plus L-NAME. INDO did not have any significant effect on the relaxant response of both compounds. The combination of L-NAME plus INDO only abolished the oleanolic acid-induced relaxation. The present results suggest that the mechanism of relaxation seems to be mainly mediated by the endothelial production of NO; however, other mechanisms cannot be excluded. It can be concluded that oleanolic acid and erythrodiol may have interesting therapeutic potential as new vasodilator drugs, thus protecting the cardiovascular system. Therefore, the intake of 'orujo' olive oil, as a source of these compounds, might be beneficial in this regard.