학술논문
Dietary plant bioactives to prevent pathologies: Olive oil polyphenols and endogenous vitamin E. Red-fleshed apples to control carcinogen-induced colon-cancer rat model
Document Type
Dissertation/Thesis
Author
Source
TDX (Tesis Doctorals en Xarxa)
Subject
616.3
Language
English
Abstract
La aceituna y el aceite de oliva virgen son uno de los ingredientes fundamentales que definen a la Dieta Mediterránea, definida en la década de los años 60 a partir del patrón alimentario de los habitantes de la isla de Creta (“The Seven Countries Study”). Por otra parte, aunque la manzana no era una fruta habitual en la isla de Creta, no deja de ser una fruta que como tal forma parte de la Dieta Mediterránea. Además, es consumida a nivel mundial, está disponible durante todo el año y es asequible económicamente. En las últimas décadas, los genetistas de plantas han trabajado y trabajan en la mejora de nuevas variedades de manzana de pulpa roja (“red-fleshed apples”) para hacerlas más atractivas para su consumo, en base a la presencia de antocianos en la pulpa. La presente Tesis Doctoral se ha centrado en tres objetivos: Objetivo 1. Evaluar el impacto de la suplementación de dieta con los principales compuestos fenólicos de la aceituna/aceite de oliva sobre la concentración de antioxidantes endógenos (α-tocoferol) en músculo e hígado. Objetivo 2. Estudiar durante dos campañas consecutivas el perfil fitoquímico (compuestos fenólicos, antocianos, triterpenos, ácidos orgánicos y ácido ascórbico) de nuevas variedades de manzana de pulpa roja obtenidas mediante mejora varietal, utilizando como referencia diferentes variedades de manzana de pulpa blanca ('Golden Smoothee', 'Granny Smith'...). Objetivo 3. Determinar el impacto de la suplementación de la dieta con manzana de pulpa roja, utilizando como referencia manzana de pulpa blanca, sobre el desarrollo y progresión del cáncer de colon (CC), inducido químicamente en un modelo murino. En relación al Objetivo 1, se ha realizado suplementación de la dieta en modelo de rata Wistar con compuestos fenólicos de oliva (oleuropeína, hidroxitirosol y secoiridoides), de tomillo, y con una combinación de estos (5 mg/kg de peso/día), durante un periodo de 21 días. Los principales resultados han mostrado que la dieta suplementada con algunos compuestos fenólicos de oliva y tomillo aumentó de forma significativa la concentración de α-tocoferol en hígado de ratas hembras. Además, se ha observado un efecto sinérgico en la combinación de fenoles de oliva y de tomillo. Este incremento de la concentración hepática de α-tocoferol observado sugiere el potencial de la suplementación dietética con compuestos fenólicos, como estrategia para el control de la enfermedad hepática más común en la actualidad, la hepatopatía grasa no alcohólica. En relación al Objetivo 2, los resultados han mostrado que las variedades de manzana “redfleshed” estudiadas contienen una cantidad de flavanoles más baja, una concentración de ácidos orgánicos similar a la variedad ‘Granny Smith’, y una mayor concentración de antocianos (cianidina-3-O-galactósido) e dihidrocalconas (floretin xilosil-glucósido), en comparación a las variedades de pulpa blanca. Además, se ha detectado un importante efecto campaña en la concentración de los diferentes compuestos fenólicos en todas las variedades de manzana estudiadas. Aunque el efecto campaña difiere entre la piel y la pulpa. A diferencia de otros metabólitos secundarios, la variación inter-campaña de antocianos en las manzanas de pulpa roja no mostró una relación clara con las condiciones climáticas del año (pluviometría y temperatura media). En cuanto al modelo experimental de CC (Objetivo 3), llevado a cabo en ratas macho Wistar, los resultados han mostrado que la suplementación de dieta con ‘Golden Smoothee’ (pulpa blanca) consigue una inhibición del 41.3% de focos con criptas aberrantes (lesión preneoplásica CC). Por otra parte, los niveles de mucina colónica se han mantenido normales por efecto de la suplementación con ‘Golden Smoothee’ y con cianidina-3-O-galactósido (principal antociano de la manzana). Estos resultados refuerzan el refrán Galés "An apple a day keeps the doctor away" en la prevención del desarrollo de cáncer de colon.
The olive and virgin olive oil are one of the fundamental ingredients that characterize the Mediterranean Diet, defined in the 1960s from the eating habits of the inhabitants of the island of Crete (“The Seven Countries Study”). On the other hand, even though the apple was not an usual fruit on the island of Crete, it is still a fruit that as such is part of the Mediterranean Diet. Also, it is consumed worldwide, it is available all year round and it is economically affordable. In recent decades, plant geneticists have worked and are still working on the improvement of new varieties of red-fleshed apples which are more attractive for consumption, due to their red-pink flesh colour as consequence of the presence of anthocyanins in the flesh. This present Doctoral Thesis has focused on three objectives: Objective 1. Evaluate the impact of dietary supplementation with the main phenolic compounds of olive/olive oil on the concentration of endogenous antioxidants (α-tocopherol) in the muscle and in the liver. Objective 2. Study for two consecutive harvest seasons the phytochemical profile (phenolic compounds, anthocyanins, triterpenes, organic acids and ascorbic acid) of new varieties of redfleshed apples obtained through varietal improvement, using as reference different varieties of white-fleshed apples ('Golden Smoothee', 'Granny Smith'...). Objective 3. Tackle the impact of dietary supplementation with red-fleshed apples, using as a reference white-fleshed apples, on the development and progression of colon cancer (CC), chemically induced in a murine model. As regards as Objective 1, dietary supplementation has been carried out in the Wistar rat model with olive phenolic compounds (oleuropein, hydroxytyrosol and secoiridoides), thyme, and with a combination of these (5 mg /kg body weight /day), for a period of 21 days. The main results have shown that the supplemented diet with some phenolic compounds of olive and thyme have significantly increased the concentration of α-tocopherol in the liver of female rats. In addition, a synergistic effect was observed in the combination of olive and thyme phenols. The observed increase in the hepatic concentration of α-tocopherol suggests the potential of the dietary supplementation with phenolic compounds, as a strategy for the control of the currently most common liver disease: the non-alcoholic fatty liver disease. In relation to Objective 2, the results have shown that the “red-fleshed” apple varieties studied contain a lower amount of flavanols, a concentration of organic acids similar to the 'Granny Smith' variety, and a higher concentration of anthocyanins (cyanidin-3-O-galactoside) and dihydrocalcones (phloretin xylosyl glycoside), compared to white-fleshed cultivars. Besides, an important season effect has been detected in the concentration of the different phenolic compounds in all the apple varieties studied. Even though, the harvest season effect differed between the skin and the flesh part. Unlike other secondary metabolites, the inter-season variation of anthocyanins in red-fleshed apples has not shown a clear relationship with the climatic conditions of the year (rainfall and average temperature). Regarding the experimental model of CC (Objective 3), carried out in male Wistar rats, the results have shown that the dietary supplementation with 'Golden Smoothee' (white-fleshed) achieves a 41.3% inhibition of foci with aberrant crypts (preneoplastic lesion CC). On the other hand, the levels of colonic mucin have remained normal as a result of the supplementation with ‘Golden Smoothee’ and with cyanidin-3-O-galactoside (main anthocyanin of apples). These results reinforce the Welsh saying "An apple a day keeps the doctor away" in preventing the development of colon cancer.
The olive and virgin olive oil are one of the fundamental ingredients that characterize the Mediterranean Diet, defined in the 1960s from the eating habits of the inhabitants of the island of Crete (“The Seven Countries Study”). On the other hand, even though the apple was not an usual fruit on the island of Crete, it is still a fruit that as such is part of the Mediterranean Diet. Also, it is consumed worldwide, it is available all year round and it is economically affordable. In recent decades, plant geneticists have worked and are still working on the improvement of new varieties of red-fleshed apples which are more attractive for consumption, due to their red-pink flesh colour as consequence of the presence of anthocyanins in the flesh. This present Doctoral Thesis has focused on three objectives: Objective 1. Evaluate the impact of dietary supplementation with the main phenolic compounds of olive/olive oil on the concentration of endogenous antioxidants (α-tocopherol) in the muscle and in the liver. Objective 2. Study for two consecutive harvest seasons the phytochemical profile (phenolic compounds, anthocyanins, triterpenes, organic acids and ascorbic acid) of new varieties of redfleshed apples obtained through varietal improvement, using as reference different varieties of white-fleshed apples ('Golden Smoothee', 'Granny Smith'...). Objective 3. Tackle the impact of dietary supplementation with red-fleshed apples, using as a reference white-fleshed apples, on the development and progression of colon cancer (CC), chemically induced in a murine model. As regards as Objective 1, dietary supplementation has been carried out in the Wistar rat model with olive phenolic compounds (oleuropein, hydroxytyrosol and secoiridoides), thyme, and with a combination of these (5 mg /kg body weight /day), for a period of 21 days. The main results have shown that the supplemented diet with some phenolic compounds of olive and thyme have significantly increased the concentration of α-tocopherol in the liver of female rats. In addition, a synergistic effect was observed in the combination of olive and thyme phenols. The observed increase in the hepatic concentration of α-tocopherol suggests the potential of the dietary supplementation with phenolic compounds, as a strategy for the control of the currently most common liver disease: the non-alcoholic fatty liver disease. In relation to Objective 2, the results have shown that the “red-fleshed” apple varieties studied contain a lower amount of flavanols, a concentration of organic acids similar to the 'Granny Smith' variety, and a higher concentration of anthocyanins (cyanidin-3-O-galactoside) and dihydrocalcones (phloretin xylosyl glycoside), compared to white-fleshed cultivars. Besides, an important season effect has been detected in the concentration of the different phenolic compounds in all the apple varieties studied. Even though, the harvest season effect differed between the skin and the flesh part. Unlike other secondary metabolites, the inter-season variation of anthocyanins in red-fleshed apples has not shown a clear relationship with the climatic conditions of the year (rainfall and average temperature). Regarding the experimental model of CC (Objective 3), carried out in male Wistar rats, the results have shown that the dietary supplementation with 'Golden Smoothee' (white-fleshed) achieves a 41.3% inhibition of foci with aberrant crypts (preneoplastic lesion CC). On the other hand, the levels of colonic mucin have remained normal as a result of the supplementation with ‘Golden Smoothee’ and with cyanidin-3-O-galactoside (main anthocyanin of apples). These results reinforce the Welsh saying "An apple a day keeps the doctor away" in preventing the development of colon cancer.