ES2239908B1 - USE OF REFINED CENTRIFUGATION ORUJO OIL AS A RETAINER OF ATEROSCLEROSIS. - Google Patents
USE OF REFINED CENTRIFUGATION ORUJO OIL AS A RETAINER OF ATEROSCLEROSIS.Info
- Publication number
- ES2239908B1 ES2239908B1 ES200400755A ES200400755A ES2239908B1 ES 2239908 B1 ES2239908 B1 ES 2239908B1 ES 200400755 A ES200400755 A ES 200400755A ES 200400755 A ES200400755 A ES 200400755A ES 2239908 B1 ES2239908 B1 ES 2239908B1
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- ES
- Spain
- Prior art keywords
- refined
- oil
- atherosclerosis
- centrifugal
- pomace
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
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- 235000010382 gamma-tocopherol Nutrition 0.000 description 1
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 1
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- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Mycology (AREA)
- Botany (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Food Science & Technology (AREA)
- Medical Informatics (AREA)
- Vascular Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Nutrition Science (AREA)
- Urology & Nephrology (AREA)
- Polymers & Plastics (AREA)
- Alternative & Traditional Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Utilización de aceite de orujo de centrifugación refinado como retardador de la aterosclerosis. El objeto de la invención es la aplicación nutricional-farmacológica del aceite de orujo de oliva de centrifugación refinado. Se describe la influencia del aceite de orujo de centrifugación refinado sobre el desarrollo de la lesión arteriosclerótica, para considerar a este aceite como alimento funcional ya que presenta unas propiedades sanitarias más allá de su función nutricional al ser un alimento natural destinado a mejorar el estado de poblaciones con riesgo de aterosclerosis.Use of refined centrifugal pomace oil as a retarder of atherosclerosis. The object of the invention is the nutritional-pharmacological application of refined centrifugal olive pomace oil. The influence of refined centrifugal pomace oil on the development of arteriosclerotic lesion is described, to consider this oil as a functional food since it has sanitary properties beyond its nutritional function as it is a natural food intended to improve the state of populations at risk of atherosclerosis.
Description
Utilización de aceite de orujo de centrifugación refinado como retardador de la aterosclerosis.Use of centrifugal pomace oil Refined as a retarder of atherosclerosis.
El objeto de la invención es la aplicación nutricional-farmacológica del aceite de orujo de oliva de centrifugación refinado. Se describe la influencia del aceite de orujo de centrifugación refinado sobre el desarrollo de la lesión arteriosclerótica, para considerar a este aceite como alimento funcional ya que presenta unas propiedades sanitarias más allá de su función nutricional al ser un alimento natural destinado a mejorar el estado de poblaciones con riesgo de aterosclerosis.The object of the invention is the application Nutritional-Pharmacological Pomace Oil Refining centrifugal olive. The influence of the refined centrifugal pomace oil on the development of the arteriosclerotic lesion, to consider this oil as functional food since it has more sanitary properties beyond its nutritional function to be a natural food intended to improve the status of populations at risk of atherosclerosis
El aceite de orujo de oliva es el que se obtiene a partir de los residuos de las aceitunas, una vez extraído el aceite de oliva virgen por presión. Mediante métodos mecánicos es posible separar el aceite de oliva virgen de las otras fases de la pasta de aceitunas, tanto líquida (alpechín) como sólidas (orujo). El orujo contiene todo el aceite no extraído por la centrifugación, denominándose alperujo. Tradicionalmente, este aceite ha sido siempre recuperado mediante el empleo de hexano. Se obtiene así un aceite de orujo de oliva crudo, que posteriormente se refina, obteniéndose aceite de orujo de oliva refinado que se puede consumir encabezado con aceite de oliva virgen.Olive pomace oil is what you get from the olives residues, once the virgin olive oil by pressure. By mechanical methods it is possible to separate virgin olive oil from the other phases of the olive paste, both liquid (alpechin) and solid (pomace). The pomace contains all the oil not extracted by centrifugation, called alperujo. Traditionally, this oil has been always recovered by using hexane. You get a crude olive pomace oil, which is subsequently refined, obtaining refined olive pomace oil that can be consume header with virgin olive oil.
En la patente de invención publicada como ES 2
048 667 (Oleícola El Tejar) se da a conocer un procedimiento para
la extracción de aceite de orujo de oliva sin utilización de
disolventes orgánicos, denominado de 2ª centrifugación ó de repaso
[J. Alba Mendoza, F. Hidalgo Casado, Mª A. Ruíz Gómez, F. Martinez
Roman, Mª J. Moyano Pérez, A. Cert Ventulá, Mª C.
Pérez-Camino y Mª V. Rúiz-Méndez.
"Características de los aceites de oliva de primera y segunda
centrifugación" Grasas y aceites, 47. 163-181
(1996)]. Ciertos aceites obtenidos mediante dicho procedimiento,
denominados "de segunda centrifugación" ó "repaso", una
vez refinados, presentan las siguientes
característi-
cas:In the invention patent published as ES 2 048 667 (Oleícola El Tejar) a process for the extraction of olive pomace oil without the use of organic solvents, known as 2nd centrifugation or review [J.] Alba Mendoza, F. Hidalgo Casado, Mª A. Ruíz Gómez, F. Martinez Roman, Mª J. Moyano Pérez, A. Cert Ventulá, Mª C. Pérez-Camino and Mª V. Rúiz-Méndez. "Characteristics of first and second centrifugal olive oils" Fats and oils, 47. 163-181 (1996)]. Certain oils obtained by said procedure, called "second centrifugation" or "review", once refined, have the following characteristics
cas:
Acidez: \leq 0,3Acidity: ≤ 0.3
Indice de peróxidos (meq. O_{2}/Kg) max: \leq 5Peroxide index (meq. O2 / Kg) max: \ leq 5
Restos de disolventes (mg/Kg) = 0,0Solvent remains (mg / kg) = 0.0
Alcoholes alifáticos (mg/Kg): \geq 1000Aliphatic alcohols (mg / kg): ≥ 1000
Ceras (mg/kg): 3000-6000Waxes (mg / kg): 3000-6000
Acidos grasos saturados en sn-2: \leq 2,0%Saturated fatty acids in sn-2: ? 2.0%
Tocoferoles totales (mg/kg): \geq 200Total tocopherols (mg / kg): ≥ 200
Eritrodiol+uvaol (mg/Kg): \geq 200Erythrodiol + uvaol (mg / Kg): ≥ 200
Esteroles totales (mg/Kg): \geq 1600Total sterols (mg / Kg): ≥ 1600
Ácido oleanólico (mg/Kg): \geq 50Oleanolic acid (mg / kg): ≥ 50
Ácido maslínico (mg/Kg): \geq 100Maslinic acid (mg / kg): ≥ 100
Un aceite de orujo de estas características es el que se ha empleado en la presente invención.A pomace oil of these characteristics is which has been used in the present invention.
El objeto de la presente invención es la utilización de aceite de orujo de centrifugación refinado en la preparación de un alimento funcional retardador de la ateroesclerosis. Asimismo dicho aceite de orujo se puede emplear en la preparación de nutraceúticos o de fitofármacos con el mismo propósito e incluso en la preparación de un medicamento retardador de la ateroesclerosis.The object of the present invention is the use of refined centrifugal pomace oil in the preparation of a functional food retardant of the atherosclerosis Also said pomace oil can be used in the preparation of nutraceuticals or phytopharmaceuticals with the same purpose and even in the preparation of a retarding medication of atherosclerosis.
El aceite de orujo de centrifugación refinado se puede utilizar para dicho propósito tal cual se obtiene o bien encabezándolo con hasta un 5% de aceite de oliva virgen. Es igualmente posible el añadir al aceite de orujo de centrifugación refinado, encabezado o no con aceite de oliva virgen, cantidades complementarias de otros compuestos, en particular tocoferoles hasta llegar a una cantidad total de al menos 1000 mg de tocoferoles totales por cada Kg de aceite y de ácido oleanólico hasta un total de 100 ppm.The refined centrifugal pomace oil is you can use for that purpose as it is obtained or topping it with up to 5% virgin olive oil. Is also possible to add to the oil of centrifugal pomace refined, headed or not with virgin olive oil, quantities complementary to other compounds, in particular tocopherols until you reach a total amount of at least 1000 mg of tocopherols Totals for each kg of oil and oleanolic acid up to a total 100 ppm
El efecto retardador de la ateroesclerosis se manifiesta a través de la disminución de triglicéridos y de lipoproteínas VLDL y HDL en ratones carentes de apolipoproteína E y también a través de la disminución de leucocitos circulantes en sangre que expresan la integrina Mac-1 en esos mismos ratones.The retarding effect of atherosclerosis is manifests through the decrease of triglycerides and of VLDL and HDL lipoproteins in mice lacking apolipoprotein E and also through the decrease of circulating leukocytes in blood expressing the mac-1 integrin in those same mice.
Fig 1. Perfil de lipoproteínas plasmático obtenido por FPLC en los ratones carentes de apo E con las diferentes dietas. Fracciones 4-8 15 corresponden a TRL, 9-17 a LDL y fracciones 18-24 a HDL.Fig 1. Plasma lipoprotein profile obtained by FPLC in mice lacking apo E with the different diets . Fractions 4-8 15 correspond to TRL, 9-17 to LDL and fractions 18-24 to HDL.
Fig 2. Porcentaje de leucocitos que expresan Mac-1 tras la administración de las diferentes dietas. Mediante citometría de flujo, se calculó el porcentaje de leucocitos que expresaron la integrina Mac-1 (CD11b) tras la tinción con un anticuerpo monoclonal marcado con fluorescencia.Fig 2. Percentage of leukocytes expressing Mac-1 after administration of the different diets . By flow cytometry, the percentage of leukocytes expressing the Mac-1 integrin (CD11b) after staining with a fluorescently labeled monoclonal antibody was calculated.
Fig 3. Áreas de lesiones aórticas de los ratones carentes de apo E alimentados con las diferentes dietas. Resultados son media \pm SEM de cada grupo. Los análisis estadísticos se efectuaron mediante la U de Mann-Whitney.^{a,b}, p< 0.05 vs control y oliva, respectivamente.Fig 3. Areas of aortic lesions of mice lacking apo E fed with different diets . Results are mean ± SEM of each group. Statistical analyzes were performed using Mann-Whitney U. a, b, p <0.05 vs control and olive, respectively.
El objeto de la presente invención es la utilización del aceite de orujo de centrifugación refinado como retardador de la ateroesclerosis, por tanto como alimento funcional según la recomendación de la European Commission Concerted Action on Functional Food Science in Europe (FUFOSE), quien en la actualidad pretende definir y caracterizar los alimentos funcionales como alimentos que consumidos en cantidades normales en la dieta habitual tienen efectos beneficiosos para la salud. En este sentido, el aceite de orujo de centrifugación refinado es un alimento natural, obtenido en condiciones en las que no se añade ni quita ningún componente mediante medios tecnológicos o biológicos, diferente del que contenga en su extracción natural y que posee propiedades que ayudan a disminuir el riesgo de padecer arteriosclerosis. Se define como "Cardiorujo de oliva" al aceite referido anteriormente a la vista de los resultados obtenidos en ratones transgénicos, concretamente ratones carentes de la apolipoproteína E (apo E knock-out).The object of the present invention is the use of refined centrifugal pomace oil as atherosclerosis retarder, therefore as a functional food according to the recommendation of the European Commission Concerted Action on Functional Food Science in Europe (FUFOSE), who in the currently aims to define and characterize food functional as foods that consumed in normal amounts in The usual diet has beneficial health effects. In In this sense, refined centrifugal pomace oil is a natural food, obtained in conditions where neither remove any component by technological or biological means, different from what it contains in its natural extraction and that it has properties that help reduce the risk of suffering arteriosclerosis. It is defined as "Olive Cardiorujo" oil referred to above in view of the results obtained in transgenic mice, specifically lacking mice of apolipoprotein E (apo E knock-out).
La tecnología transgénica ha generado una serie de ratones muy útiles para el estudio de la hiperlipidemia y de la arteriosclerosis que se añaden a las ventajas que poseen estos modelos animales tales como la economía en su mantenimiento, ya que requieren pequeñas cantidades tanto de alimento como de agentes de ensayo. Adicionales ventajas son su fácil reproducción en un corto periodo de tiempo y la disponibilidad de razas puras con fenotipos heredables perfectamente conocidos.Transgenic technology has generated a series of mice very useful for the study of hyperlipidemia and arteriosclerosis that are added to the advantages of these animal models such as the economy in its maintenance, since they require small amounts of both food and agents test. Additional advantages are its easy reproduction in a short time period and availability of pure breeds with phenotypes Inheritable perfectly known.
Trabajando con estos animales se está delimitando la influencia de componentes ambientales y genéticos en el desarrollo del proceso arteriosclerótico, más concretamente en los procesos celulares y moleculares que intervienen en el mismo. Ha sido precisamente la generación de ratones modificados genéticamente que presentan lesiones vasculares complejas lo que ha permitido disponer de un sistema de referencia para evaluar la progresión o el retraso de la enfermedad vascular en presencia de diferentes proteínas o agentes ambientales (Functional Food Science in Europe. (1998). British Journal of Nutrition, 80(1):S1-S193). Estos ratones, sin los cuales todo este progreso sería imposible, son los ratones carentes de la apolipoproteína E (apo E knock-out). Además, en ellos se ha desarrollado una estandarizada metodología para evaluar el grado de lesión que permite cuantificar exactamente la contribución de un agente (Osada J, Joven J, Maeda N. The value of apolipoprotein E knockout mice for studying the effects of dietary fat and cholesterol on atherogenesis. Curr. Opin. Lipidol. 2000;11(1):25-9).Working with these animals is defining the influence of environmental and genetic components in the development of the arteriosclerotic process, more specifically in the cellular and molecular processes involved in it. He has been precisely the generation of modified mice genetically presenting complex vascular lesions what has allowed to have a reference system to evaluate the progression or delay of vascular disease in the presence of different proteins or environmental agents (Functional Food Science in Europe. (1998). British Journal of Nutrition, 80 (1): S1-S193). These mice, without the which all this progress would be impossible, are the mice lacking of apolipoprotein E (apo E knock-out). Further, in them a standardized methodology has been developed to assess the degree of injury that allows to quantify exactly the contribution of an agent (Osada J, Young J, Maeda N. The value of apolipoprotein E knockout mice for studying the effects of dietary fat and cholesterol on atherogenesis. Curr. Opin. Lipidol 2000; 11 (1): 25-9).
Los ratones carentes de la apolipoproteína E, alimentados con una dieta comercial estándar baja en grasa (4%) y con un 0.01% (p/p) de colesterol, muestran unos niveles de colesterol de 500 mg/dl, mientras que los animales sanos, en las mismas condiciones, se mantienen en 75 mg/dl (Knowles JW, Maeda N. Genetic modifiers of atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2000;20(11):2336-2345 y Plump AS, Smith JD, Hayek T, Aaltosetala K, Walsh A, Verstuyft JG, et al. Severe Hypercholesterolemia and Atherosclerosis in Apolipoprotein-E-Deficient Mice Created by Homologous Recombination in ES Cells. Cell 1992;71(2):343-353). Esta elevación de los niveles de colesterol plasmático se debe principalmente al aumento del colesterol transportado por las VLDL, IDL y LDL. El ratón deficiente en apo E, con una dieta normal, desarrolla una extensa aterosclerosis fibroproliferativa espontánea (Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein-E. Science 1992;258(5081):468-471 y Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R. Apo E-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb 1994;14:133-140). Un análisis cronológico de esta aterosclerosis muestra la misma secuencia de formación de la lesión que la ya establecida en otros modelos animales y en el hombre. Las lesiones se extienden por el entramado arterial, formándose en primer lugar en la base de la aorta y en las arterias coronarias proximales, para continuar luego a lo largo de toda la aorta, con una predisposición especial en los puntos de ramificación de los vasos mayores: las arterias carótidas, las intercostales, las mesentéricas, las renales y las iliacas.Mice lacking apolipoprotein E, fed a standard low-fat commercial diet (4%) and with 0.01% (w / w) cholesterol, show cholesterol levels of 500 mg / dl, while healthy animals , under the same conditions, they are maintained at 75 mg / dl (Knowles JW, Maeda N. Genetic modifiers of atherosclerosis in mice. Arterioscler Thromb Vasc Biol 2000; 20 (11): 2336-2345 and Plump AS, Smith JD, Hayek T , Aaltosetala K, Walsh A, Verstuyft JG, et al . Severe Hypercholesterolemia and Atherosclerosis in Apolipoprotein-E-Deficient Mice Created by Homologous Recombination in ES Cells. Cell 1992; 71 (2): 343-353). This rise in plasma cholesterol levels is mainly due to the increase in cholesterol carried by VLDL, IDL and LDL. The mouse deficient in apo E, with a normal diet, develops an extensive spontaneous fibroproliferative atherosclerosis (Zhang SH, Reddick RL, Piedrahita JA, Maeda N. Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein-E. Science 1992; 258 (5081) : 468-471 and Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R. Apo E-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb 1994; 14: 133-140). A chronological analysis of this atherosclerosis shows the same sequence of lesion formation as that already established in other animal models and in man. The lesions extend through the arterial network, forming firstly at the base of the aorta and in the proximal coronary arteries, to then continue along the entire aorta, with a special predisposition at the branching points of the major vessels. : the carotid, intercostal, mesenteric, renal and iliac arteries.
Con estos animales se estudiará la influencia sobre el desarrollo de la lesión arteriosclerótica del aceite de orujo de centrifugación refinado.With these animals the influence will be studied on the development of arteriosclerotic lesion of the oil of refined centrifugal pomace.
A continuación se definen las características del insaponificable del aceite empleado procedente de Oleícola El Tejar de la campaña 2002-2003:The characteristics are defined below. of the unsaponifiable oil used from Oleícola El Roof of the 2002-2003 campaign:
Acidez: 0.1Acidity: 0.1
Índice de peróxidos (meq. O_{2}/kg) max: \leq 5Peroxides index (meq. O2 / kg) max: \ leq 5
Restos de disolventes (mg/kg) 0,00Solvent remains (mg / kg) 0.00
Ceras (mg/kg): 3484Waxes (mg / kg): 3484
Alcoholes alifáticos (mg/kg): 3117Aliphatic alcohols (mg / kg): 3117
Ácidos grasos saturados en sn-2: 2,0%Saturated fatty acids in sn-2: 2.0%
Tocoferoles totales (mg/kg): 468Total tocopherols (mg / kg): 468
- \alpha-tocoferol (mg/kg): 386-? -tocopherol (mg / kg): 386
- \beta-tocoferol (mg/kg): 38-? -tocopherol (mg / kg): 38
- \gamma-tocoferol (mg/kg): 44- γ-tocopherol (mg / kg): 44
Eritrodiol+uvaol (mg/kg): 507Erythrodiol + uvaol (mg / kg): 507
Esteroles totales (mg/Kg): 2245Total sterols (mg / Kg): 2245
Ácido oleanólico (mg/kg): 59Oleanolic acid (mg / kg): 59
Ácido maslínico (mg/kg): 107Maslinic acid (mg / kg): 107
Saponificable del aceite:Saponifiable oil:
Laúrico C.12
\dotlNDLauric C.12
\ dotlND
Mirístico C.14
\dotl0,02Myristic C.14
\ dotl0.02
Palmitico C.16
\dotl10,29Palmitic C.16
\ dotl10.29
Palmitoleico C.16:1
\dotl0,76Palmitoleic C.16: 1
\ dotl0.76
Esteárico C.18
\dotl2,95Stearic C.18
\ dotl2.95
Oleico C.18:1
\dotl74,27Oleico C.18: 1
\ dotl74.27
Linoleico C.18:2
\dotl8,07Linoleic C.18: 2
\ dotl8.07
Linolénico C. 18:3
\dotl0,70Linolenic C. 18: 3
\ dotl0.70
Aráquico C.20
\dotl0,45Aráquico C.20
\ dotl0.45
Gadoleico C.20:1
\dotl0,33Gadoleico C.20: 1
\ dotl0.33
Behénico C.22:1
\dotl0,17Behenic C.22: 1
\ dotl0.17
Erúcico C.22:1
\dotlNDErutic C.22: 1
\ dotlND
Lignocérico C.24
\dotl0.07Lignoceric C.24
\ dotl0.07
Se utilizaron ratones machos híbridos de C57BL/6J y 1290la carentes de apo E homozigotos descendientes de los generados por Piedrahita y cols. (Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci USA 1992;89:4471-4475) y se mantuvieron en la Unidad Mixta de Investigación de Zaragoza, España. A 26 animales de dos meses de edad se les puso en ayuno durante 18 horas. Se les anestesió con isofluorano y se obtuvo su sangre por punción retroorbital para la determinación de colesterol plasmático. Se dividieron al azar en tres grupos de idéntico nivel de colesterol y se mantuvieron en jaulas estériles provistas de filtro en habitaciones con ciclos de 12 horas de luz y las mismas de oscuridad. Los animales tuvieron libre acceso al agua y a la comida. El pienso fue suministrado por Harlan Teklad (Harlan Ibérica, Barcelona). Se hizo un seguimiento del peso de los animales a lo largo del estudio y ninguno de los animales murió durante el estudio. El protocolo fue aprobado por el Comité ético para la experimentación animal de la Universidad de Zaragoza.Hybrid male mice of C57BL / 6J and 1290la lacking apo E homozygous descendants of those generated by Piedrahita et al. (Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci USA 1992; 89: 4471-4475) and remained in the Unit Mixed Research of Zaragoza, Spain. 26 animals of two Months of age were fasted for 18 hours. They are anesthetized with isofluorane and his blood was obtained by puncture retroorbital for the determination of plasma cholesterol. Be randomly divided into three groups of identical cholesterol level and they were kept in sterile cages fitted with a filter in rooms with cycles of 12 hours of light and the same as darkness. The animals had free access to water and food. The feed was supplied by Harlan Teklad (Harlan Iberian, Barcelona). The weight of the animals throughout the study and none of the animals died during the study The protocol was approved by the Ethics Committee for animal experimentation of the University of Zaragoza.
Los tres grupos recibieron: a) la dieta del ratón para el grupo control, b) la dieta del ratón suplementada con un 10% (p/p) de aceite de oliva virgen de reciente preparación y c) la dieta del ratón enriquecida con un 10% (p/p) de aceite de orujo. Las dietas se prepararon semanalmente y se almacenaron en atmósfera de N_{2} a 20ºC. Las dietas se suministraron durante 11 semanas y fueron bien toleradas.The three groups received: a) the diet of mouse for the control group, b) the mouse diet supplemented with 10% (w / w) of freshly prepared virgin olive oil and c) The mouse diet enriched with 10% (w / w) pomace oil. The diets were prepared weekly and stored in an atmosphere of N2 at 20 ° C. The diets were supplied for 11 weeks and They were well tolerated.
Tras 10 semanas de la dieta, Se tomaron muestras retroorbitales de los animales previamente ayunados y anestesiados con isofluorano. Aproximadamente 1 x 10^{6} leucocitos, se resuspendieron en PBS que contenía 0.1% (w/v) BSA y 10 mmol/l azida sódica. En ellos se estudió la expresión de Mac-1 (CD11b) por citometría de flujo. Los datos se expresan como porcentaje de células marcadas positivamente.After 10 weeks of the diet, samples were taken retroorbitals of previously fasted and anesthetized animals with isofluoran. Approximately 1 x 10 6 leukocytes are resuspended in PBS containing 0.1% (w / v) BSA and 10 mmol / l azide Sodium In them the expression of Mac-1 was studied (CD11b) by flow cytometry. The data is expressed as percentage of positively labeled cells.
Finalizado el periodo experimental los animales fueron sacrificados con una inyección de avertina (Aldrich Chemical Co., Madrid, España) y se obtuvo la sangre por punción cardiaca. Las concentraciones plasmáticas de colesterol total y de triglicéridos se midieron enzimáticamente en placas de microensayo usando kits de Sigma Chemical Co. (Madrid, España) y Boehringer Mannheim GMBH (Barcelona, España). Como control de calidad del proceso se utilizó cardiolipid (Sigma). Para un análisis más detallado de los perfiles lipoproteicos, una mezcla de 100 \mul de plasma de los animales de cada grupo se sometió a cromatografía líquida de filtración por gel en una columna de Superosa 6B (Pharmacia LKB Biotechnology, Barcelona, España) de acuerdo con las condiciones descritas por Calleja y coas (Low-cholesterol and high-fat diets reduce atherosclerotic lesion development in ApoE-knockout mice. Arterioscler Thromb Vasc Biol 1999;19(10):2368-2375). Se recogieron fracciones de 0.5 ml y se midió el colesterol total como se ha descrito anteriormente.End of the experimental period the animals were sacrificed with an injection of avertin (Aldrich Chemical Co., Madrid, Spain) and blood was obtained by cardiac puncture. Plasma concentrations of total cholesterol and of triglycerides were measured enzymatically in microassay plates using kits from Sigma Chemical Co. (Madrid, Spain) and Boehringer Mannheim GMBH (Barcelona, Spain). As a quality control of Cardiolipid (Sigma) process was used. For one more analysis Detailed of the lipoprotein profiles, a mixture of 100 µl Plasma of the animals in each group underwent chromatography liquid gel filtration on a Superosa 6B column (Pharmacia LKB Biotechnology, Barcelona, Spain) in accordance with the conditions described by Calleja and coas (Low-cholesterol and high-fat diets reduce atherosclerotic lesion development in ApoE-knockout mice. Arterioscler Thromb Vasc Biol 1999; 19 (10): 2368-2375). They were collected 0.5 ml fractions and total cholesterol was measured as previously described.
El corazón y el sistema circulatorio arterial se perfundió con tampón fosfato formalina (4% pH 7.4 Panreac, Barcelona, España) a presión fisiológica. Los corazones y las aortas fueron diseccionados, limpiados y almacenados en formaldehído neutro. La zona de las aurículas y la base de la aorta se extrajeron para su análisis y se transfirieron a un tubo con OCT (Bayer Diagnostic, Germany) donde se mantuvieron 24 horas para eliminar burbujas. Los corazones se situaron sobre la base de un criostato (Microm HM505E, Barcelona España) con OCT nuevo. Se recogieron cortes seriados de la aorta proximal y del seno aórtico, se tiñeron con Sudan IV B (Sigma Chemical Company), y un teñido de contraste con hematoxilina y eosina (Sigma Chemical Company). La evaluación morfométrica se realizó según el método de Paigen y cols. (Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 1987;68:231-240) tomando el tamaño medio de la lesión de las cuatro secciones, que comprenden desde la región proximal aórtica hasta el seno aórtico que contenía las tres válvulas completas. Las lesiones fueron capturadas utilizando un microscopio Canon con una videocámara conectada a un ordenador. La cuantificación de la lesión aterosclerótica y el perímetro de los vasos se realizaron con el software NIH Image.The heart and arterial circulatory system are perfused with phosphate formalin buffer (4% pH 7.4 Panreac, Barcelona, Spain) under physiological pressure. The hearts and the Aortas were dissected, cleaned and stored in neutral formaldehyde The atrial area and the base of the aorta they were removed for analysis and transferred to a tube with OCT (Bayer Diagnostic, Germany) where they stayed 24 hours to Remove bubbles The hearts were placed on the basis of a cryostat (Microm HM505E, Barcelona Spain) with new OCT. Be collected serial cuts of the proximal aorta and aortic sinus, stained with Sudan IV B (Sigma Chemical Company), and a dye of contrast with hematoxylin and eosin (Sigma Chemical Company). The Morphometric evaluation was performed according to the Paigen method and cols. (Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 1987; 68: 231-240) taking size middle of the lesion of the four sections, which comprise from the proximal aortic region to the aortic sinus that contained the three full valves The lesions were captured using a Canon microscope with a camcorder connected to a computer. The quantification of atherosclerotic lesion and the perimeter of glasses were made with NIH Image software.
Los datos fueron analizados con el programa Instat para Windows (GraphPad). La mayoría de los parámetros en este estudio no siguen una distribución normal de acuerdo con el test de Shapiro-Wilk. Así pues, para el análisis estadístico se realizó el test de la U Mann-Whitney para los datos no apareados. Las diferencias se consideraron no significativas cuando P>0.05. La asociación entre variables se realizó por el cálculo del coeficiente de correlación de Spearman.The data were analyzed with the program Instat for Windows (GraphPad). Most of the parameters in this study does not follow a normal distribution according to the Shapiro-Wilk test. So, for the analysis The Mann-Whitney U test was performed for unpaired data. The differences were considered not significant when P> 0.05. The association between variables is performed by calculating the correlation coefficient of Spearman
Después de 11 semanas de administración de las
dietas, no se observaron cambios en el peso corporal en los
diferentes grupos (Tabla I). Tampoco se observaron cambios en el
peso del hígado por el enriquecimiento graso de las dietas. Tal
como se muestra en la tabla, el colesterol plasmático no
experimentó variaciones significativas en ninguna de las
intervenciones dietéticas, en concordancia con resultados previos
al aportar el contenido de lo grasa del 10% a estos animales. Ni el
colesterol transportado en HDL, ni los triglicéridos plasmáticos
aparecieron afectados en el grupo de aceite de oliva y si
aparecieron disminuidos en el grupo de animales alimentados con el
aceite de
orujo.After 11 weeks of dietary administration, no changes in body weight were observed in the different groups (Table I). Nor were changes in liver weight due to fatty enrichment of the diets. As shown in the table, plasma cholesterol did not experience significant variations in any of the dietary interventions, in accordance with previous results by providing the fat content of 10% to these animals. Neither the cholesterol transported in HDL, nor the plasma triglycerides were affected in the olive oil group and if they appeared diminished in the group of animals fed with the oil of
Marc.
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
La distribución del colesterol plasmático entre las diferentes lipoproteínas plasmáticas fue analizado por cromatografía líquida en una columna de Superose 6B y se muestra en la figura 1. El grupo que recibió el aceite de oliva presentó mayores niveles de lipoproteínas LDL en tanto que el grupo que recibió el aceite de orujo presentó menores niveles de lipoproteínas VLDL y HDL en consonancia con la disminución de triglicéridos (principalmente transportados en VLDL) y el descenso de HDL verificado por el método de precipitación que se presentó en la tabla I. Estos resultados indican que los componentes que diferencian a ambos aceites poseen suficiente potencia para cambiar el comportamiento de los parámetros lipídicos en estos animales.The distribution of plasma cholesterol between the different plasma lipoproteins was analyzed by Liquid chromatography on a Superose 6B column and shown in Figure 1. The group that received the olive oil presented higher levels of LDL lipoproteins while the group that received pomace oil presented lower levels of VLDL and HDL lipoproteins in line with the decrease in triglycerides (mainly transported in VLDL) and descent of HDL verified by the precipitation method presented in Table I. These results indicate that the components that differentiate both oils possess enough power to change the behavior of lipid parameters in these animals.
Se analizó el porcentaje de leucocitos circulantes en sangre que expresan Mac-1 para ver la activación de estas células. Debido a que esta integrina permite la interacción de los monocitos circulantes con las moléculas ICAM-1 y 2 del endotelio y así su migración a los focos ateroscleróticos, es una diana importante en el desarrollo de la arteriosclerosis. En la figura 2 se muestra el porcentaje de leucocitos que expresan Mac-1 en los grupos de ratones que consumieron las dietas control, enriquecida en oliva o en orujo. Tal como se aprecia el último grupo presentó los valores más bajos de células potencialmente reclutables comparados con las otras dos dietas.The percentage of leukocytes was analyzed circulating in blood expressing Mac-1 to see the activation of these cells. Because this integrin allows the interaction of circulating monocytes with molecules ICAM-1 and 2 of the endothelium and thus its migration to the atherosclerotic foci, is an important target in the development of arteriosclerosis Figure 2 shows the percentage of leukocytes expressing Mac-1 in the groups of mice that consumed control diets, enriched in olive or in pomace. As you can see the last group presented the values lower potentially recruitable cells compared to Two other diets
En la figura 3 se muestran los valores cuantitativos de las lesiones ateroscleróticas en los animales tras el consumo de las diferentes dietas. Los animales cuya dieta estuvo enriquecida en el aceite de oliva presentaron mayores valores de lesión que el grupo control. En contraste, el grupo que recibió el aceite de orujo presentó valores significativamente más bajos que los animales alimentados con las otras dos dietas.The values are shown in Figure 3 Quantitative atherosclerotic lesions in animals after The consumption of different diets. The animals whose diet was enriched in olive oil had higher values of injury than the control group. In contrast, the group that received the Pomace oil presented significantly lower values than the animals fed with the other two diets.
Estos resultados globalmente indican que los componentes presentes en el aceite de orujo ensayado tienen suficiente potencia para disminuir el desarrollo de la aterosclerosis en los ratones deficientes en la apolipoproteína E y que en este proceso están implicados procesos celulares tales como la activación de Mac-1 en leucocitos circulantes junto con cambios de triglicéridos circulantes y en menor proporción de lipoproteínas de alta densidad, puesto que el perfil de este último parámetro (descenso de colesterol en HDL) observado para el aceite de orujo fue hallado de características negativas. El aceite de orujo fue perfectamente tolerado por todos los animales y no tuvo repercusiones de sobrepeso, ni aumento de masa hepática en las dosis administradas.These results globally indicate that components present in the pomace oil tested have enough power to decrease the development of the atherosclerosis in mice deficient in apolipoprotein E and that cellular processes such as Mac-1 activation in circulating leukocytes along with circulating triglyceride changes and in minor proportion of high density lipoproteins, since the profile of this last parameter (cholesterol decrease in HDL) observed for pomace oil it was found of negative characteristics. Pomace oil was perfectly tolerated by all animals and had no repercussions of overweight or increase in mass liver in the doses administered.
Claims (6)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200400755A ES2239908B1 (en) | 2004-03-26 | 2004-03-26 | USE OF REFINED CENTRIFUGATION ORUJO OIL AS A RETAINER OF ATEROSCLEROSIS. |
| PCT/ES2005/070036 WO2005092354A1 (en) | 2004-03-26 | 2005-03-23 | Use of refined, centrifuged pomace oil as an atherosclerosis inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200400755A ES2239908B1 (en) | 2004-03-26 | 2004-03-26 | USE OF REFINED CENTRIFUGATION ORUJO OIL AS A RETAINER OF ATEROSCLEROSIS. |
Publications (2)
| Publication Number | Publication Date |
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| ES2239908A1 ES2239908A1 (en) | 2005-10-01 |
| ES2239908B1 true ES2239908B1 (en) | 2006-12-16 |
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| Application Number | Title | Priority Date | Filing Date |
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| ES200400755A Expired - Fee Related ES2239908B1 (en) | 2004-03-26 | 2004-03-26 | USE OF REFINED CENTRIFUGATION ORUJO OIL AS A RETAINER OF ATEROSCLEROSIS. |
Country Status (2)
| Country | Link |
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| ES (1) | ES2239908B1 (en) |
| WO (1) | WO2005092354A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2246603B1 (en) * | 2002-07-03 | 2007-06-16 | Consejo Sup. De Investig. Cientificas | PROCEDURE FOR THE PREPARATION OF HYDROXYTIROSOL ESTERS, ESTERS OBTAINED AND USE. |
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2004
- 2004-03-26 ES ES200400755A patent/ES2239908B1/en not_active Expired - Fee Related
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- 2005-03-23 WO PCT/ES2005/070036 patent/WO2005092354A1/en active Application Filing
Non-Patent Citations (3)
| Title |
|---|
| COVAS, M.I. et al.: "Bioavailability of tyrosol, an antioxidant phenolic compound present in wine and olive oil, in humans", Drugs Exptl. Clin. Res., (2003), Vol. XXIX (5/6), páginas 203-206, todo el documento. * |
| COVAS, M.I. et al.: "Virgin olive oil phenolic compounds: binding to human low density lipoprotein (LDL) and effect on LDL oxidation", Int. J. Clin. Pharm. Res., (2000), Vol. XX (3/4), páginas 49-54, todo el documento, en particular, resumen. * |
| MANGIAPANE, E.H. et al.: "Modulation of the regression of atherosclerosis in the hamster by dietary lipids: comparison of coconut oil and olive oil", British J. Nutr., (1999), Vol. 82, páginas 401-409, todo el documento. * |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2239908A1 (en) | 2005-10-01 |
| WO2005092354A1 (en) | 2005-10-06 |
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