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Reduction in Hypercholesterolemia and Risk Of GRASAS Y ACEITES, 61 (4), OCTUBRE-DICIEMBRE, 378-389, 2010, ISSN: 0017-3495 DOi:10.3989/gya.021210 Reduction in hypercholesterolemia and risk of cardiovascular diseases by mixtures of plant food extracts: a study on plasma lipid profile, oxidative stress and testosterone in rats By Doha A. Mohamed, Thanaa E. Hamed and Sahar Y. Al-Okbi * Food Sciences and Nutrition Department, National Research Centre, Dokki, Cairo, Egypt (*Corresponding author: S_Y_alokbi@ hotmail.com) RESUMEN cias mostraron una mejora del perfil lipídico del plasma, un significativo incremento en la testosterona, y un descenso Reducción de las enfermedades cardiovasculares e del estrés oxidativo con una prometedora prevención de las hipercolesterolemia por mezclas de extractos de plan- enfermedades cardiovasculares y ateroesclerosis. El efecto tas comestibles: un estudio del perfil lipídico, estrés anti-aterogénico de las mezclas de los extractos puede ser oxidativo y testosterona en ratas. debida a la presencia de compuestos fenólicos, fitoesteroles, tocoferoles y ácidos grasos insaturados. El presente estudio fue dirigido a preparar y evaluar ia in- fluencia de dos mezclas de extractos de plantas comestibles PALABRAS CLAVE: Estrés oxidativo - Hipereolesterole- sobre ei perfil lipídico del plasma, estrés oxidativo y nivel de mia - Mezclas de extraetos - Perfil lipfdieo - Testosterona. testosterona en ratas alimentadas con una dieta hipercoieste- rolemica. La salubridad de las mezclas de extractos estudia- das fue evaluada mediante la determinación de las funciones Summary del hígado y dei riñon. El contenido totai de fenoles, tocofero- les, ácidos grasos, y materia insaponificable (UNSAP) fueron Reduction in hypercholesterolemia and risk of determinado en la mezclas de extractos. Las ratas fueron ali- cardiovascular diseases by mixtures of plant food extract: mentadas con dietas hipercoiesterolémica junto con una do- a study on plasma lipid profile, oxidative stress and sis oral diaria de (300 mg/kg de peso) cada mezcla I y II du- testosterone in rats. rante un mes y comparada con un control hipercolesterolémico y un control normal. Los resultados muestran que el conteni- The present study was postulated to prepare and evaluate do de a-tocopherol fue 0.750 y 4.017 mg, y-tocopherol fue the influence of two plant food extract mixtures on plasma lipid 0.564 mg y O y 5-tocopherol fue 15.23mg y 0.634mg/100g de profile, oxidative stress and testosterone levels in rats fed a mezcla I y II, respectivamente. El contenido de fenoles en las hypercholesterolemic diet. The safety of the studied extract mezcla I and II fue 36.74 y 23.72 g equivalentes de ácido mixtures was evaluated through the determination of liver and gálico/1 OOg de mezcla, respectivamente. La investigación por kidney functions. The total phenolic contents, tocopherols, GLC de UNSAP reveló que el estigmasterol y el ß-sitosterol fatty acids and unsaponifiable matter (UNSAP) in the extract fueron los principales fitoesteroles de las mezclas I y II, res- mixtures were determined. Rats fed a hypercholesterolemic pectivamente seguido por el campesterol en ambos casos. El diet were given a daily oral dose (300 mg/kg rat body weight) análisis por GLC de ios ácidos grasos mostró que el ácido of either mixture I or II for a month and compared with a oleico fue el ácido graso mayoritario en ambas mezclas de control hypercholesterolemic group and a normal control extractos. Los resultados con animales de experimentación group. Results showed that a-tocopherol was 0.750 and 4.017 mostraron que la alimentación con dietas hipercolesterolémi- mg, Y-tocopherol was 0.564 mg and 0 and 5-tocopherol was cas produce un incremento significativo en los lípidos totales, 15.23mg and 0.634mg/100g for mixtures I and II, respectively. colesterol total (T-Ch), triglicéridos (TGs), colesterol en lipo- The phenolic contents in mixtures I and II were 36.74 and proteínas de baja densidad (LDL-Ch), en las relaciones T-Ch/ 23.72 g gallic acid equivalent/1 OOg mixture, respectively. The HDL-Ch y TGs/HDL-Ch y malondialdehido (MDA) y una signi- GLC investigation of UNSAP revealed that stigmasterol and ficativa reducción en el colesterol de ias iipoproteínas de alta ß-sitosterol were the major phytosterols in mixtures I and II, densidad (HDL-Ch), vitamina E, ß-caroteno and testosterona. respectively followed by campesterol in both. The GLC analysis Las ratas alimentadas con dietas hipercolesteroiémicas junto of the fatty acids showed that oleic acid was the major fatty acid con mezclas I y II mostraron una mejora significativa del perfil in both extract mixtures. Results from the animal experiment lipídico del plasma comparado con ei grupo control hypercho- showed that feeding a hypercholesterolemic diet produced lesterolémico. Esta mejora estuvo asociada con una significa- a significant increase in total lipids, total cholesterol (T-Ch), tiva reducción del estrés oxidativo reflejado por la elevación triglycérides (TGs), low density lipoprotein cholesterol (LDL- de los niveles de antioxidantes en el plasma (vitamin E y ß- Ch), T-Ch/HDL-Ch, TGs/HDL-Ch and malondialdehyde (MDA) carotene) y reducción de los niveles de MDA en plasma. Los and a significant reduction in high density lipoprotein cholesterol niveles de testosterona en plasma aumentaron significativa- (HDL-Ch), vitamin E, ß-carotene and testosterone. Rats fed mente en ratas alimentadas con dietas hipercolesteroiémicas a hypercholesterolemic diet and given mixture I or II showed junto con mezclas I y II en comparación con el control hiper- significant improvements in plasma lipid profile compared to colesteroiémico. La testosterona del plasma mostró una co- the hypercholesterolemic control group. This improvement rrelación negativa significativa con los TGs y TGs/HDL-Ch en was associated with a significant reduction in oxidative stress ratas control hipercolesteroiémicas. Las mezclas de los ex- reflected by an elevation in plasma levels of antioxidants tractos estudiados mostraron una completa salubridad hacia (vitamin E and ß-carotene) and a reduction in plasma MDA las funciones del hígado y el riñon. En conclusión las mez- levels. The plasma level of testosterone increased significantly 378 REDUCTION IN HYPERCHOLESTEROLEMIA AND RISK OF CARDIOVASCULAR DISEASES BY MIXTURES OF PLANT FOOD... in the rats fed the hypercholesterolemic diet and given mixture triglycérides, low levels of high-density lipoprotein I or II compared to the hypercholesterolemic control. Plasma cholesterol), and a pro-inflammatory and thrombogenic testosterone showed a significant negative correlation with state (Saad and Gooren, 2009). The effects of plasma TGs and TGs/HDL-Ch in the hypercholesteroiemic control rats. The studied extract mixtures showed complete physiological doses of testosterone seem to have safety towards liver and kidney functions. In conclusion less impact on the parameters of lipid metabolism. the tested extract mixtures showed an improvement in the However, supraphysiological levels of testosterone plasma lipid profile, a significant increase in testosterone can lower HDL levels (Schubert and Jockenhövel, and a decrease in oxidative stress with promising prevention 2010). The relationship between androgen deficiency of atherosclerosis and cardiovascular diseases. The anti- and atherosclerosis is complex, poorly understood, atherogenic effect of the extract mixtures may be due to the presence of phenolic compounds, phytosterols, tocopherols and remains controversial. Studies in animals and unsaturated fatty acids. and humans suggest that androgen deficiency is associated with increased TGs, T-Ch, and LDL- KEY-WORDS: Extract mixtures - Hypereholesterolemia Ch. Although the effects of androgen deficiency on - Lipid protile - Oxidative stress - Testosterone. HDL-Ch remains controversial, recent data suggest reduced levels and androgen therapy are associated with increased levels of HDL-Ch and may improve 1. INTRODUCTION reverse cholesterol transport. Furthermore, androgen treatment of hypogonadal men significantly improved Cardiovascular diseases (CVD) including coronary lipid profiles. Emerging data indicate that androgens heart disease and stroke are the leading cause of play an important role in lipid metabolism. Androgen mortality in both developed and developing countries, treatment results in a favorable lipid profile, suggesting accounting for roughly 20% of all worldwide deaths that androgens may provide a protective effect against per year (Thomas and Rich, 2007). Therefore, the development and/or progression of atherosclerosis hypereholesterolemia and its associated CVD (Traisheia/., 2009). represent one of the greatest worldwide economic, Oxidative stress plays an important role in the social and medical challenges that we are facing initiation and progression of atherosclerosis by now (Olshansky et ai, 2005). The large majority stimulating inflammation and promoting cytokine of epidemiological studies have demonstrated that production (Fernández-Robredo et ai, 2008). elevated plasma triglycérides and/or reduced plasma Diet plays an important role in the maintenance of HDL-Ch concentrations are associated with increased optimal cardiovascular health (Dauchet et ai, 2009). cardiovascular risk (Poli etal., 2008). An abnormal ratio Consumption of fruits and vegetables is associated of triglycérides to HDL-Ch indicates an atherogenic with lower concentrations of total and low-density lipid profile and a risk for the development of coronary lipoprotein cholesterol and with a lowered
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