Redução do marcador inflamatório TNF-α após consumo de semente de linhaça por coelhos hipercolesterolemicos / Decrease in the inflammatory marker TNF-a after comsumption of flaxseed by hypercholesterolemic rabbits

Background: Functional foods such as flaxseed have been commonly consumed to prevent atherosclerosis. Objectives: To assess the effects of flaxseed in atherogenesis in rabbits consuming a high-cholesterol diet. Methods: Thirty male albino rabbits were randomized to three groups based on a 12-week dietary treatment: control group (G1), standard diet; high-cholesterol diet (G2), standard diet plus 0.25% cholesterol from lyophilized eggs; and high-cholesterol plus flaxseed (G3), similar diet as G2 plus flaxseed. Biochemical (total cholesterol [TC], high-density lipoprotein [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) and immunohistochemical (intercellular adhesion molecule 1 [ICAM-1] and tumor necrosis factor alpha [TNF- α ]) analyses were performed in all groups. P values < 0.05 indicated statistical significance. Results: At 12 weeks, serum TC levels increased significantly in G2 and G3 compared with G1. Serum LDL-C levels were higher in group G2, and the increase in group G3 was approximately six times lower than that in G2. HDL-C levels increased in all groups, with the highest increase observed in G2. Triglycerides levels in G3 decreased by ~70% and differed significantly in G1 and G3 (p = 0.034) and G2 and G3 (p = 0.015). ICAM-1 levels increased only in aortic segment 4 in G3. TNF- α levels in G3 were similar to those in the control group, while the levels in G2 were greater than twice as those in the control group (p < 0.05). Conclusions: The group fed with a functional diet (flaxseed) showed decreased development of atherosclerosis, reduced serum triglycerides levels, and lower TNF- α levels on immunohistochemistry

Fundamentos: Alimentos funcionais, como a linhaça, têm sido consumidos com frequência para prevenção da aterosclerose. Objetivos: Avaliar os efeitos da linhaça sobre a aterogênese em coelhos submetidos a uma dieta rica em colesterol. Métodos: Trinta coelhos albinos machos foram randomizados em três grupos com base em um tratamento dietético por 12 semanas: grupo controle (G1), dieta padrão; dieta rica em colesterol (G2), dieta padrão mais 0,25% de colesterol proveniente de ovos liofilizados; e dieta rica em colesterol mais linhaça (G3), dieta semelhante à do G2 adicionada de linhaça. Análise bioquímica (colesterol total [CT], lipoproteína de alta densidade [HDL-colesterol], lipoproteína de baixa densidade [LDL-colesterol] e triglicérides) e imunohistoquímica (molécula de adesão intercelular 1 [ICAM-1] e fator de necrose tumoral alfa [TNF- α ]) foram realizadas em todos os grupos. Valores de p < 0,05 indicaram significância estatística. Resultados: Às 12 semanas, os níveis séricos de CT aumentaram significativamente nos grupos G2 e G3 em comparação com o G1. Os níveis séricos de LDL-colesterol foram mais altos no grupo G2, e o aumento no grupo G3 foi cerca de seis vezes menor do que no G2. Os níveis de HDL-colesterol aumentaram em todos os grupos, com o maior aumento observado no G2. Os níveis de triglicérides no G3 reduziram em ~70% e diferiram significativamente entre o G1 e G3 (p = 0,034) e G2 e G3 (p = 0,015). Níveis de ICAM-1 aumentaram apenas no segmento aórtico 4 no G3. Os níveis de TNF- α no grupo G3 foram semelhantes aos do grupo controle, enquanto os níveis no G2 foram maiores do que o dobro em relação aos do grupo controle (p < 0,05). Conclusões: O grupo alimentado com uma dieta funcional (linhaça) mostrou redução no desenvolvimento de aterosclerose, níveis séricos mais baixos de triglicérides e níveis mais baixos de TNF- α à imunohistoquímica

Oferta y composición nutricional de ensaladas en patios de comida de centros comerciales de Lima Metropolitana, 2014 / Supply and nutritional composition of salads in the food courts of shopping centers of Metropolitan Lima, 2014

Evaluar la oferta y composición nutricional de las ensaladas ofrecidas como plato principal en los patios de comida de los centros comerciales de Lima, Perú. Materiales y métodos. Se revisó las cartas de comida de todas las franquicias presentes en los patios de comida de los once centro comerciales de Lima, luego se evaluó la composición nutricional de las ensaladas ofertadas como plato principal calculando su contenido calórico, proteico, carbohidratos, grasas, colesterol, fibra y sodio, y la adecuación de ingesta para una cena (30% de una dieta de 2000 kcal). Resultados. Las ensaladas como plato principal representaron el 4,7% de la oferta, solo 7/17 franquicias ofrecían al menos una ensalada. El costo promedio de las ensaladas fue superior a los otros platos ($5,3 vs 4,7; p<0,001). El contenido calórico promedio fue de 329 kcal y de 2,7 g de fibra; con relación a una cena, se encontró un alto porcentaje de adecuación proteica (172,9%), de colesterol (121,0%), y bajo para calorías (54,8%), carbohidratos (23,1%) y fibra (36,4%). Conclusiones. Las ensaladas que se ofertan en patios de centros comerciales de Lima son escasas y más costosas, presentan poco aporte de fibra y altos contenidos de colesterol. Se deben revisar estrategias para mejorar la accesibilidad de ensaladas de calidad en escenarios donde solo ofertan comidas rápidas...

To assess supply and nutritional composition of the salads offered as an entrée main course in the food courts of the shopping centers in Lima, Peru. Materials and methods. The menus of all food franchises present in the food courts of the eleven shopping centers of Lima were reviewed. The nutritional composition of salads offered as an entrée were calculated for calories, protein content, carbohydrates, fats, cholesterol, fiber and sodium, and the adequacy of intake for a dinner (30% of a diet of 2000 kcal). Results. Salads as entrées accounted for 4.7% of the supply, and only 7 out of 17 franchises offered at least one salad. The average cost of the salads was higher than the other dishes ($5.3 vs $4.7; p<0.001). The average calorie content was 329 kcal and 2.7 g fiber; in relation to a dinner, we found a high percentage of adequacy for protein (172.9%), cholesterol (121.0%), and low adequacy for calories (54.8%), carbohydrates (23.1%) and fiber (36.4%). Conclusions. The salads that are offered in food courts in the shopping centers of Lima are scarce and more expensive, have little fiber content and are high in cholesterol. Strategies should be reviewed to improve the accessibility of quality salads offered in areas where only fast food is offered...

Relación de ácidos grasos omega 6/omega 3 / Omega 6/omega 3 fatty acid ratio

La relación de ácidos grasos (AG)ω6/ω3 de la dieta contemporánea favorece a los AG ω6. El objetivo del estudio fue evaluar el efecto de dietas con cantidades crecientes de aceite de pescado (AcP), rico en AG ω3, sobre el crecimiento y las variables hematológicas de ratas macho recien destetadas de la cepa Sprague-Dawley. Los animales consumieron por un período de 31 días dietas que contenían AcP o aceite de ajonjolí (AcA) incorporado a 5, 10 ó 15% (pxp). Se observó un déficit del crecimiento como de la ingesta de alimento en los grupos que consumieron AcP. La concentración de hemoglobina (Hb) disminuyó en relación al incremento (>5% pxp) del AcP dietario. Siendo el AcP una fuente pobre de AG ω6, planteamos que la deficiencia parcial de la serie polienoica ω6 que resultó al incrementar las cantidades de AcP dietario pueden afectar el crecimiento y la eritropoyesis(AU)

The ω6/ω3 fatty acid (FA) ratio of our contemporary diet favors ω6 over ω3 FA. The object of the study was to evaluate the effect of increasing amounts of dietary fish oil, rich in ω3 FA, on growth and hematological variables of the weanling male Sprague-Dawley rat. Animals were fed diets containing either fish oil (FO) or sesame oil (SO) at 5, 10 or 15% (w/w) for 31 d. Growth retardation and reduced food intake was observed in groups fed FO. Hemoglobin (Hb) concentration diminished when the dietary FO was above 5% (w/w). FO is a poor source of ω6 fatty acids. We postulate that a partial deficiency in ω6 polyenic family, is a consequence of the increasing amounts of FO in the diets, that may affect growth and erytropoiesis. In this report we show evidence supporting the hypothesis that diets enriched with fish oil can alter normal growth and induced hematological changes in the male weanling rat(AU)

Aumento da imunorreatividade da molécula de adesão intercelular-1 na esclera e coroide em modelo experimental de hipercolesterolemia / Increased intercellular adhesion molecule-1 immunoreactivity in the sclera-choroid complex in hypercholesterolemia experimental model

Objetivo: O objetivo deste trabalho é avaliar a expressão da molécula de adesão intercelular-1 (ICAM-1) na esclera e coroide de coelhos hipercolesterolêmicos. Métodos: Coelhos New Zealand foram organizados em dois grupos: GN (grupo dieta normal), composto por 8 coelhos (8 olhos), recebeu ração padrão para coelhos, durante 4 semanas; GH (grupo hipercolesterolêmico), composto por 13 coelhos (13 olhos), recebeu dieta rica em colesterol a 1% por 8 semanas. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 4ª semana para o GN e 8ª semana para o GH foi realizada a eutanásia dos animais. Os olhos foram corados com hematoxilina-eosina e submetidos à análise histológica, histomorfométrica e imunohistoquímica com o anticorpo ICAM-1. Resultados: Observou-se significativo aumento do colesterol total e triglicerídeos do GH em relação ao GN (p<0,001). A avaliação histológica com hematoxilina eosina revelou grande quantidade de macrófagos no complexo esclero-coroidal do GH. No GH constatou-se significativo aumento da espessura da esclera e coroide em relação ao GN (p<0,001). Houve significativo aumento da expressão da ICAM-1 na esclera e coroide dos animais do GH em relação ao GN (p<0,001). Conclusão: Este estudo demonstra que a dieta hipercolesterolêmica induz ao aumento da expressão da ICAM-1 na esclera e coroide de coelhos. .

Objective: The aim of this study is to investigate the expression of the intercellular adhesion molecule 1 (ICAM-1) in the sclera and choroid of hypercholesterolemic rabbits Methods: New Zealand rabbits were divided into two groups: the normal diet group (NG), with 8 rabbits (8 eyes), was fed a standard rabbit diet for 4 weeks; the hypercholesterolemic group (HG), with 13 rabbits (13 eyes), was fed a 1% cholesterol- enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the start of the experiment and at the euthanasia time. HG and NG animals were euthanized after 8th week and 4th week, respectively. Their eyes were stained with hematoxylin-eosin and underwent histological, histomorphometric and immunohistochemical analyses with ICAM-1 antibody. Results: The diet has induced a significant increase in total cholesterol and triglyceride levels in HG when compared with NG (p<0.001). The histological analysis with hematoxylin-eosin revealed a large number of macrophages in the HG sclera-choroid complex. Moreover, a significant increase in the HG sclera and choroid thickness was observed in relation to NG (p<0.001). There was a significant increase in the ICAM-1 expression in HG sclera and choroid in relation to NG Conclusion: This study has revealed that the hypercholesterolemic diet induces an increase in the ICAM-1 expression in the rabbits’ sclera and choroid. .

Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits / Expressão das citocinas TNF-α and IL-6 na coroide e esclera de coelhos hipercolesterolêmicos

Purpose: This study aimed to evaluate the expression of the inflammatory cytokines TNF-α and IL-6 in the sclera and choroid of hypercholesterolemic rabbits. Method: Twenty-one New Zealand male albino rabbits were divided into two groups: NG and HG. The NG group was fed a standard rabbit diet and the HG group was fed a cholesterol-enriched diet (1%). The serum total cholesterol, triglyceride, HDL cholesterol, and fasting blood glucose levels were determined at the beginning of the experiment and on the day of euthanasia. Euthanasia of animals in the NG and HG groups was performed at the end of the 4th and 8th week, respectively. The eyes were analyzed immunohistochemically using TNF-α and IL-6 antibodies. Results: At the time of euthanasia, the HG group showed a significant increase in total cholesterol and triglyceride when compared with the NG group (p<0.001). When compared with the NG group, there was a significant increase in the expression of TNF-α (p<0.001) and IL-6 (p=0.002) in the choroid and sclera of animals in the HG group. Conclusion: This study demonstrates that the hypercholesterolemic diet induces expression of TNF-α and IL-6 in the choroid and sclera of rabbits. .

Objetivo: Avaliar a expressão das citocinas inflamatórias TNF-α e IL-6 na esclera e coroide de coelhos hipercolesterolêmicos. Método: Coelhos New Zealand foram organizados em dois grupos: GN recebeu ração padrão para coelhos; GH recebeu dieta rica em colesterol a 1%. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 4ª semana para o GN e 8ª semana para o GH foi realizada a eutanásia dos animais. Os olhos foram submetidos à análise imuno-histoquímica com os anticorpos TNF-α e IL-6. Resultados: O GH manifestou significativo aumento do colesterol total e triglicerídeos em relação ao GN (p<0,001). Houve significativo aumento da expressão da TNF-α (p<0,001) e da IL-6 (p=0,002) na coroide e esclera dos animais do GH em relação ao GN. Conclusão: Este estudo demonstra que a dieta hipercolesterolêmica induz ao aumento da expressão das citocinas TNF-α e IL-6 na coroide e esclera de coelhos. .

Hypercholesterolemic diet induces hepatic steatosis and alterations in mRNA expression of NADPH oxidase in rat livers / Dieta hipercolesterolemiante induz esteatose hepática e alterações na expressão de mRNA da NADPH oxidase em fígados de ratos

Objective : This study aimed to determine whether a hypercholesterolemic diet induces hepatic steatosis, alterations in mRNA expression of NADPH oxidase subunits, and antioxidant defenses.Materials and methods : Fischer rats were divided into two groups of eight animals according to the treatment, control (C) and hypercholesterolemic diet (H). Those in group C were fed a standard diet (AIN-93M), and those of the group H were fed a hypercholesterolemic diet (25% soybean oil and 1% cholesterol).Results : The hypercholesterolemic diet did not affect body weight, but resulted in the accumulation of lipids in the liver, increased serum activities of aminotransferases and cholesterol levels. Biomarker of lipid peroxidation (TBARS) and mRNA expression of NADPH oxidase subunits p22phox and p47phox were increased in the liver of animals in group H. Besides, the activity and expression of antioxidant enzymes were altered.Conclusion : The results show increased mRNA expression of NADPH oxidase subunits and changes in antioxidant enzyme activities in diet-induced hepatic steatosis. Arq Bras Endocrinol Metab. 2014;58(3):251-9.

Objetivo Determinar se uma dieta hipercolesterolemiante induz esteatose hepática, alterações na expressão de mRNA da NADPH oxidase e nas defesas antioxidantes.Materiais e métodos : Ratas Fischer foram divididas em dois grupos de oito animais de acordo com o tratamento recebido, controle (C) e hipercolesterolêmico (H). Aquelas do grupo C foram alimentadas com dieta padrão (AIN-93M) e as do grupo H foram alimentadas com dieta hipercolesterolemiante (25% de óleo de soja e 1% de colesterol). As dietas foram oferecidas por oito semanas.Resultados : O grupo H apresentou acúmulo de lipídios no fígado, aumento das atividades de ALT e AST e da concentração de colesterol no soro comparado ao grupo C. O marcador da peroxidação lipídica (TBARS) e os níveis de mRNA das subunidades p47phox da NADPH-oxidase e p22phox foram aumentados no fígado de animais do grupo H, além de alteração da atividade e expressão de enzimas antioxidantes.Conclusão : Os resultados mostram um aumento na expressão de subunidades da NADPH oxidase e alterações na atividade das enzimas antioxidantes na esteatose hepática induzida por dieta hipercolesterolemiante. Arq Bras Endocrinol Metab. 2014;58(3):251-9.

Effects of the kefir and banana pulp and skin flours on hypercholesterolemic rats

PURPOSE: To investigate the effect of kefir and banana pulp and skin flours on the serum levels of total cholesterol, HDL-c, LDL-c and triacylglycerols in rats fed cholesterol-rich diet. METHODS: Thirty Male Wistar rats were used. In the first 21 days, the animals were fed purified hypercholesterolemic diets, except the standard group. In the next 21 days, the animals were given modified diets: Group GC: standard diet AIN-93G; Group HIP: hypercholesterolemic diet; Group F: hypercholesterolemic diet added of 1% of banana skin flour and 7% of banana pulp flour; Group Q: hypercholesterolemic diet plus kefir suspension by oral infusion (1.5 ml/animal); Group FQ: hypercholesterolemic diet added of 1% banana skin flour and 7% of banana pulp flour plus kefir suspension (1.5 ml/animal). RESULTS: In spite of the high fiber content, the addition of banana pulp (7%) and skin (1%) flour did not alter the plasma levels of total cholesterol, HDL-c and LDL-c. However, they reduced the TG levels in 22%. Already fermented kefir reduced significantly the levels of VLDL, LDL-c and triacylglycerols, in addition to having increased HDL-c. However, it was not possible to verify the symbiotic effect between both. CONCLUSION: The results reinforce the beneficial effects of kefir in reducing the risks of cardiovascular diseases.

High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.

Aumento da imunorreatividade ao VEGFR-1 no complexo coroido-escleral em modelo experimental de hipercolesterolemia / Increased VEGFR-1 immunoreactivity in the choroid-scleral complex in hypercholesterolemia experimental model

OBJETIVO: O objetivo deste trabalho é investigar a expressão do fator de crescimento vascular endotelial (VEGF) na coroide e esclera, utilizando um modelo experimental de hipercolesterolemia. MÉTODO: Coelhos New Zealand foram organizados em dois grupos: O grupo dieta normal (GN), composto por 8 coelhos (8 olhos), recebeu ração padrão para coelhos, durante 4 semanas; e o grupo hipercolesterolêmico (GH), composto por 13 coelhos (13 olhos), recebeu dieta rica em colesterol a 1% por 8 semanas. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 8ª semana para o GH e 4ª semana para o GN foi realizada a eutanásia dos animais e os olhos foram submetidos à análise imuno-histoquímica com os anticorpos RAM-11 e VEGFR-1. RESULTADOS: Observou-se significativo aumento do colesterol total e triglicerídeos do GH em relação ao GN (p<0,001). Houve significativo aumento da expressão da RAM-11 e VEGFR-1 na coroide e esclera dos animais do GH em relação ao GN (p<0,001). CONCLUSÃO: Este estudo demonstra que a dieta hipercolesterolêmica em coelhos induz ao aumento da concentração de macrófagos e da imunorreatividade ao VEGFR-1 na coroide e esclera, expressando similaridade com a degeneração macular relacionada à idade (DMRI) humana.

PURPOSE: The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF) in the choroid and sclera using hypercholesterolemia experimental model. METHODS: New Zealand rabbits were divided into two groups: 8 rabbits (8 eyes), in the normal diet group (NG), were fed by a standard diet for 4 weeks; and 13 rabbits (13 eyes), in the hypercholesterolemic group (HG), were fed by a 1% cholesterol-enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the initiation of the experiment and at the euthanasia time. After hypercholesterolemic group 8th week and NG 4th week, animals were euthanized and their eyes underwent immunohistochemical analysis with the RAM-11 and VEGFR-1). RESULTS: The diet has induced a significant increase in total cholesterol and triglyceride levels in HG when compared with NG (p<0.001). There was a significant increase in the RAM-11 and VEGFR-1 expressions in hypercholesterolemic group choroid and sclera in relation to NG (p<0,001). CONCLUSION: This study has revealed that the hypercholesterolemic diet in rabbits induces an increase in the macrophage concentration and immunoreactivity to VEGFR-1 in the choroid and sclera, resembling human age-related macular degeneration (ARMD).

Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr-/-, C57BL/6-background). Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12) or 7% pequi oil (Pequi group, N = 12) for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein) and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units). Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action.

La respuesta terapéutica a ezetimiba en ratones C57BL/6 es mediada por cambios en la expresión de NPC1L1, ABCG5 y ABCG8 en el enterocito / Therapeutic response to ezetimibe in C57BL/6 mice is mediated by changes in NPC1L1, ABCG5 and ABCG8 expression in the enterocyte

Las proteínas NPC1L1, ABCG5 y ABCG8 participan en la absorción intestinal de colesterol. Ezetimiba inhibe este proceso bloqueando a NPC1L1, sin embargo, su efecto sobre ABCG5 y ABCG8 aún no está claro. Así, el objetivo del presente trabajo fue evaluar en ratones C57BL/6 con hipercolesterolemia inducida por dieta y tratados con ezetimiba, la expresión de NPC1L1, ABCG5 y ABCG8 mediante PCR en tiempo real y Western blot, en 3 grupos de animales: 1, dieta hipercolesterolémica D12336; 2, dieta D12336 más 5 mg/kg/día de ezetimiba; 3, dieta control. El nivel sérico de colesterol total fue significativamente diferente entre los grupos estudiados (control: 1,85 +/- 0,49 mmol/L; dieta D12336: 3,11 +/- 0,73 mmol/L; ezetimiba: 2,11 +/- 0,50 mmol/L, P = 0,001). La expresión génica de NPC1L1 aumentó 5,4 veces en el grupo que recibió la dieta D12336 (P = 0,003). Por otro lado, la expresión génica de ABCG5 y ABCG8 no fue diferente en el grupo con hipercolesterolemia (P = 0,239 y P = 0,201, respectivamente). Después del tratamiento con ezetimiba, la expresión génica de ABCG5 se incrementó 15,6 veces (P = 0.038). No hubo diferencias significativas en la expresión génica de NPC1L1 (P = 0,134) y ABCG8 (P = 0,067). En relación a la expresión proteica, la dieta D12336 incrementó los niveles de expresión de NPC1L1 (P = 0,022) y ABCG5 (P = 0,008); el tratamiento con ezetimiba incrementó los niveles de NPC1L1 (P = 0,048) y redujo los niveles de ABCG5 (P = 0,036) y ABCG8 (P = 0,016). En conclusión, nuestros resultados sugieren que tanto la dieta hipercolesterolémica como el tratamiento con ezetimiba, en un modelo experimental, afectan los niveles de expresión de NPC1L1, ABCG5 y ABCG8, sugiriendo que ABCG5 y ABCG8 están involucrados en la respuesta hipolipemiante a este fármaco. No obstante, el mecanismo mediante el cual se explica esta interacción requiere de un futuro estudio.

Proteins NPC1L1, ABCG5 and ABCG8 are involved in the intestinal absorption of cholesterol. Ezetimibe inhibits this process by blocking NPC1L1, however, its effect on ABCG5 and ABCG8 is not yet clear. Thus, the objective of this study was to evaluate in C57BL / 6 mice with diet-induced hypercholesterolemia treated with ezetimibe, the expression of NPC1L1, ABCG5 and ABCG8 by real time PCR and Western blot, in 3 groups of animals: 1, diet hypercholesterolemic D12336, 2, D12336 diet plus 5 mg/kg/ day of ezetimibe, 3, diet control. The serum level of total cholesterol was significantly different between groups (control: 1.85 +/- 0.49 mmol / L; diet D12336: 3.11 +/- 0.73 mmol / L; ezetimibe: 2.11 +/- 0.50 mmol / L, P = 0.001). NPC1L1 gene expression increased 5.4-fold in the group receiving the diet D12336 (P = 0.003). Furthermore, the gene expression of ABCG5 and ABCG8 was not different in the group with hypercholesterolemia (P = 0.239 and P = 0.201, respectively). After treatment with ezetimibe, ABCG5 gene expression was increased 15.6 times (P = 0.038). No significant differences in gene expression of NPC1L1 (P = 0.134) and ABCG8 (P = 0.067). Regarding protein expression, the D12336 diet increased the levels of expression of NPC1L1 (P = 0.022) and ABCG5 (P = 0.008), treatment with ezetimibe increased the levels of NPC1L1 (P = 0.048) and reduced levels of ABCG5 (P = 0.036) and ABCG8 (P = 0.016). In conclusion, our results suggest that both hypercholesterolemic diet as treatment with ezetimibe, in an experimental model, affect the expression levels of NPC1L1, ABCG5 and ABCG8, suggesting that ABCG5 and ABCG8 are involved in lipid-lowering response to this drug. However, the mechanism by which this interaction is explained requires further study.

Aumento da expressão do MCP-1 coroidal e escleral em modelo experimental de hipercolesterolemia / Increase of choroidal and scleral MCP-1 expression in hypercholesterolemia experimental model

OBJETIVO: O objetivo deste trabalho é demonstrar experimentalmente que a dieta rica em colesterol provoca aumento da expressão da MCP-1 na coroide e esclera. MÉTODO: Coelhos New Zealand foram organizados em dois grupos: GN (grupo dieta normal), composto por 8 coelhos (8 olhos), recebeu ração padrão para coelhos, durante 4 semanas; GH (grupo hipercolesterolêmico), composto por 13 coelhos (13 olhos), recebeu dieta rica em colesterol a 1% por 8 semanas. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 8ª semana para o GH e 4ª semana para o GN foi realizada a eutanásia dos animais e os olhos foram submetidos à análise imuno-histoquímica com o anticorpo anti-MCP-1. RESULTADOS: A dieta provocou significativo aumento do colesterol total e triglicerídeos do GH em relação ao GN (p<0,001). Houve significativo aumento da expressão da MCP-1 na coroide e esclera dos animais do GH em relação ao GN (p<0,001). CONCLUSÃO: Este estudo demonstrou que a dieta hipercolesterolêmica em coelhos induz ao aumento da expressão do MCP-1 na coroide e esclera.

PURPOSE: The aim of this study is to experientially demonstrate that a cholesterol-enriched diet induces an increase in the MCP-1 expression in the choroid and sclera. METHOD: New Zealand rabbits were divided into two groups: GN (normal diet group) of 8 rabbits (8 eyes) was fed a standard rabbit diet for 4 weeks; GH (hypercholesterolemic group) of 13 rabbits (13 eyes) was fed a 1% cholesterol enriched diet for 8 weeks. Total serum cholesterol, triglyceride, HDL cholesterol and fasting blood glucose exams were performed at the start of the experiment and at the euthanasia time. After GH 8th week and GN 4th week animals were euthanized and their eyes underwent immunohistochemical analysis with the anti-MCP-1 antibody. RESULTS: The diet has induced a significant increase in GH total cholesterol and triglyceride levels when compared with NG (p<0.001). There was a significant increase in the MCP-1 expression in GH choroid and sclera in relation to GN (p<0.001). CONCLUSION: This study has revealed that the hypercholesterolemic diet in rabbits induces an increase in the MCP-1 expression in the choroid and sclera.

Resveratrol provoca efeitos antiaterogênicos em um modelo animal de aterosclerose / Resveratrol causes antiatherogenic effects in an animal model of atherosclerosis

FUNDAMENTO: O resveratrol protege o sistema cardiovascular por meio de uma série de mecanismos, incluindo atividades antioxidantes e antiplaquetárias. OBJETIVO: Avaliar os possíveis efeitos anti-inflamatórios e antiaterogênicos do resveratrol, utilizando coelhos alimentados com uma dieta hipercolesterolêmica (1 por cento de colesterol). MÉTODOS: Vinte coelhos brancos adultos do sexo masculino foram selecionados e divididos em dois grupos: grupo controle (GC), 10 coelhos; e grupo resveratrol (GR), 10 coelhos. Os animais foram alimentados com uma dieta hipercolesterolêmica por 56 dias. Para a dieta do GR, o resveratrol (2mg/kg peso/dia) foi adicionado do 33º ao 56º dia. RESULTADOS: Não houve diferença significativa entre os grupos no colesterol sérico total, no colesterol HDL, no colesterol LDL e nos triglicerídeos. No GC, 70 por cento apresentaram lesões ateroscleróticas avançadas da aorta (tipos III, IV, V ou VI). Todos os animais do GR apresentaram lesões ateroscleróticas leves da aorta (tipos I ou II) ou não apresentaram lesões. A razão entre a área intimal e a área da camada intimal/medial mostrou-se significativamente menor no GR quando comparada ao GC (p < 0,001). Áreas positivas para moléculas de adesão celular vascular-1 (VCAM-1) foram menores no GR (p = 0,007). As concentrações de proteína quimiotática de monócitos-1 (MCP-1) e de interleucina-6 (IL-6) mostraram-se significativamente menores no GR do que no GC (p = 0,039 e p = 0,015, respectivamente). CONCLUSÃO: O Resveratrol apresentou importantes efeitos antiaterogênicos e anti-inflamatórios em um modelo animal com coelhos alimentados com uma dieta hipercolesterolêmica.

BACKGROUND: Resveratrol protects the cardiovascular system by a number of mechanisms, including antioxidant and anti-platelet activities. OBJECTIVE: To assess the potential anti-inflammatory and antiatherogenic effects of resveratrol using rabbits fed a hypercholesterolemic diet (1 percent cholesterol). METHODS: Twenty white male rabbits were selected and divided into two groups: control group (CG), 10 rabbits; and resveratrol group (RG), 10 rabbits. The animals were fed a hypercholesterolemic diet for 56 days. For the RG diet, resveratrol (2mg/kg weight/day) was added from days 33 - 56. RESULTS: There was no significant difference in the total serum cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides between the groups. Of the CG, 70 percent had advanced aortic atherosclerotic lesions (types III, IV, V, or VI). All animals from the RG had mild aortic atherosclerotic lesions (types I or II, or no lesions). The intima area and the intima/media layer area ratio was significantly lower in the RG as compared to the CG (p<0.001). Positive areas for VCAM-1 molecules were lower in the RG (p=0.007). The MCP-1 and IL-6 concentrations were lower in the RG than the CG (p=0.039 and p=0.015, respectively). CONCLUSION: Resveratrol had significant anti-atherogenic and anti-inflammatory effects in an animal model with rabbits fed a hypercholesterolemic diet (1 percent cholesterol).

Efeito de duas variedades de feijão (Phaseolus vulgaris) no metabolismo lipídico de hamsters / Effect of two beans varieties (Phaseolus vulgaris) in hamster lipid metabolism

Introdução Os feijões comuns, da espécie Phaseolus vulgaris, são amplamente produzidos e consumidos no Brasil. As variedades, carioca e preto ganham destaque na região Sudeste do país. Encontra-se descrita na literatura a ação hipocolesterolemizante de algumas leguminosas, tais como, soja, tremoço e feijão caupi, que podem estar associados à redução do risco de doenças cardiovasculares. Objetivo Avaliar o potencial efeito da adição de farinhas de feijões carioca e preto (Phaseolus vulgaris) no metabolismo lipídico de hamsters alimentados com dieta contendo gordura saturada e colesterol. Métodos A produção das farinhas dos feijões envolveu as etapas de autoclavagem, congelamento, liofilização e moagem. As propriedades hipocolesterolemizantes destas farinhas foram avaliadas por meio de dois ensaios biológicos. Foram utilizados hamsters Golden Syrian, machos com 21 dias, pesando 60 ± 4g, que receberam as dietas experimentais ad libitum. No Ensaio A, os animais foram separados em 3 grupos, diferenciados pela dieta. Todas as dietas eram hipercolesterolemizantes [13.5 por cento de gordura de coco e 0.1 por cento colesterol] e tinham as mesmas quantidades de proteínas, carboidratos, fibras, vitaminas e minerais. O Grupo Controle (C) tinha como fonte protéica a caseína; no Grupo Feijão Carioca (FC) a farinha de feijão carioca representou 15 por cento do peso total da dieta e no Grupo Feijão Preto a farinha de feijão preto representou 15 por cento do peso total da dieta. No Ensaio B, os animais foram separados em três grupos novamente. Desta vez, a única diferença entre os grupos foi quanto a fonte protéica, para o grupo controle (C) somente caseína, para o grupo feijão carioca (FC), 67 por cento de feijão e 7,5 por cento de caseína e para o grupo feijão preto (FP), 62 por cento de feijão e 7,5 por cento de caseína. Nos dois ensaios, após 21 dias de experimento, foi realizada coleta de materiais biológicos (plasma, fígado e fezes). Resultados O processo de produção d...

Evaluación de efecto vasoprotector del consumo de curcumina en ratas macho Sprague-Dawley con dieta hipercolesterolémica / Evaluation of the curcumin vasoprotective effect in Sprague-Dawley male rats with a hypercholesterolemic diet

INTRODUCCIÓN: El hígado graso no alcohólico puede abarcar desde una simple esteatosis hasta una cirrosis hepática. Los mecanismos fisiopatológicos que modulan el estrés oxidativo, la actividad inflamatoria y profibrótica, deberían ser cruciales en su mayor o menor agresividad hepática y vascular. Un compuesto derivado de la Cúrcuma longa L, la curcumina, poseería propiedades vasoprotectoras. OBJETIVO: Comparar en situaciones de dieta hipercolesterolémica los cambios vasculares entre ratas macho Sprague Dawley que consumen curcumina y las que no consumen. MATERIAL Y MÉTODO: Estudio analítico, experimental, longitudinal y prospectivo en ratas macho Sprague-Dawley expuestas a condiciones de hígado graso no alcohólico e hígado graso no alcohólico adicionando curcumina, durante 4 meses. Sacrificadas, se realizó protocolo de función vascular en arteria mesentérica superior aislada (respuesta a acetilcolina, N nitro-L-arginina metil éster y nitroprusiato) y medición de presión portal por punción directa. Los resultados fueron expresados en promedios junto a la desviación estándar de la media. Lasdiferencias entre los grupos fueron probadas mediante t de Studenty test de Mann-Whitney. RESULTADOS: La medición de presión portal no mostró diferencias significativas entre ambos grupos. No hubo diferencias significativas en las pruebas con Nnitro-L-arginina metil éster ni nitroprusiato; diferencia que sí existió con acetilcolina entre la dilatación de la arteria mesentérica superior de hígado graso no alcohólico y las de hígado graso no alcohólico más curcumina. DISCUSIÓN: La curcumina mejoró la respuesta vasodilatadora a acetilcolina, lo que sugiere que el posible efecto antioxidante sería mejorando la función endotelial. Se sugiere su futuro uso terapéutico.

INTRODUCTION: Nonalcoholic fatty liver disease can range from simple steatosis to cirrhosis. The pathophysiological mechanisms that modulate oxidative stress, inflammatory and profibrotic activity should be crucial in the liver injury and vascular aggressiveness. Curcumin, a compound derived from Curcuma longa L, possesses vasoprotectives properties. OBJECTIVE: To compare in hypercholesterolemic diet situations the vascular changes between Sprague-Dawley male rats who consume curcumin and who do not consume. MATERIAL AND METHOD: Analytical, experimental, prospective and longitudinal study in Sprague-Dawley male rats exposed to conditions of Nonalcoholic fatty liver with and without curcumin, for four months. After the sacrifice, a vascular function protocol was performed on an isolated superior mesenteric artery (response to acetylcholine, L-NGNitroarginine Methyl Ester and nitroprusside) and measurement of portal pressure by direct puncture. The results were expressed as average and the standard deviation of the central tendency. The differences between the groups were tested using Student's t-test and Mann-Whitney test. RESULTS: The portal pressure measurement showed no significant differences between groups. There was no significant difference in the nitroprusside test, in the other hand, exist a difference with acetylcholine between arteries of nonalcoholic fatty liver group against nonalcoholic fatty liver plus curcumin group. DISCUSSION: Curcumin improved the vasodilator response in response to acetylcholine, suggesting a possible antioxidant effect which improves endothelial function. It is suggested for future therapeutic use.

Rosuvastatin prevents myocardial necrosis in an experimental model of acute myocardial infarction

Dyslipidemia is related to the progression of atherosclerosis and is an important risk factor for acute coronary syndromes. Our objective was to determine the effect of rosuvastatin on myocardial necrosis in an experimental model of acute myocardial infarction (AMI). Male Wistar rats (8-10 weeks old, 250-350 g) were subjected to definitive occlusion of the left anterior descending coronary artery to cause AMI. Animals were divided into 6 groups of 8 to 11 rats per group: G1, normocholesterolemic diet; G2, normocholesterolemic diet and rosuvastatin (1 mg·kg-1·day-1) 30 days after AMI; G3, normocholesterolemic diet and rosuvastatin (1 mg·kg-1·day-1) 30 days before and after AMI; G4, hypercholesterolemic diet; G5, hypercholesterolemic diet and rosuvastatin (1 mg·kg-1·day-1) 30 days after AMI; G6, hypercholesterolemic diet and rosuvastatin (1 mg·kg-1·day-1) 30 days before and after AMI. Left ventricular function was determined by echocardiography and percent infarct area by histology. Fractional shortening of the left ventricle was normal at baseline and decreased significantly after AMI (P < 0.05 in all groups), being lower in G4 and G5 than in the other groups. No significant difference in fractional shortening was observed between G6 and the groups on the normocholesterolemic diet. Percent infarct area was significantly higher in G4 than in G3. No significant differences were observed in infarct area among the other groups. We conclude that a hypercholesterolemic diet resulted in reduced cardiac function after AMI, which was reversed with rosuvastatin when started 30 days before AMI. A normocholesterolemic diet associated with rosuvastatin before and after AMI prevented myocardial necrosis when compared with the hypercholesterolemic condition.

Effect of a cholesterol rich diet, recurrent infection and possible treatment modalities on the pulmonary vascular system: an experimental study / Efecto de la dieta rica en colesterol, la infección recurrente, y las posibles modalidades de tratamiento sobre el sistema vascular pulmonar: un estudio experimental

OBJECTIVE: Infection may lead to inflammation, atherosclerosis and thrombotic vascular events. The atherosclerotic effect of hypercholesterolaemia on the vascular system is well-known. However, limited studies were done on the therapeutic and preventative agents. The aim of this study was to investigate the effects of infection and cholesterol rich diet combined with an antibiotic, anti-inflammatory agent and red wine on the pulmonary vascular system. METHODS: Fifty-nine rats were evaluated. Six groups were created: Control-Group I (n = 10); infection - Group II (n = 9), infection-cholesterol rich diet - Group III (n = 12), infection-cholesterol rich dietcefepime - Group IV (n = 11); infection-cholesterol rich diet-diclofenac potassium - Group V (n = 9); infection-cholesterol rich diet and red wine - Group VI (n = 8). Blood samples of rats were collected for cholesterol analysis every month. Sections of central pulmonary arteries were examined for thickness of the intima and medial wall by computerised image analysis. RESULTS: There was a statistically significant difference in serum cholesterol levels and in thickness of the intima between the groups (p = 0.000). The rest of the groups had more intimal thickening than Group I (p = 0.000). Group III had thicker intima than Groups IV and V (p = 0.009, p = 0.011 respectively). There was no significant difference between the groups in thickness of media (p = 0.432). CONCLUSION: Infection and cholesterol rich diet have a synergistic effect on atherosclerosis in pulmonary arteries. However, antibiotics and anti-inflammatory agents could be useful in prevention.

OBJETIVO: La infección puede conducir a inflamación, ateroesclerosis y eventos vasculares trombóticos. El efecto aterosclerótico de la hipercolesterolemia en el sistema vascular es bien conocido. Sin embargo, se hicieron estudios limitados sobre los agentes preventivos y terapéuticos. El objetivo de este estudio fue investigar los efectos de la infección y la dieta rica en colesterol, combinados con agentes antibióticos, anti-inflamatorios, y vino tinto, sobre el sistema vascular pulmonar. MÉTODOS: Cincuenta y nueve ratas fueron evaluadas. Se hicieron seis grupos: grupo-control I (n = 10), grupo-infección II (n = 9), grupo infección-dieta rica en colesterol III (n = 12), grupo-infección-dieta rica en colesterol-cefepima IV (n = 11), grupo-infección-dieta rica en colesterol-diclofenaco potásico V (n = 9), grupo-infección-dieta rica en -vino tinto VI (n = 8). Se tomaron muestras de sangre de ratas para analizar el colesterol cada mes. Se examinaron secciones de las arterias pulmonares centrales para determinar el grosor de la pared íntima y media mediante análisis computarizado de imágenes. RESULTADOS: Hubo una diferencia estadísticamente significativa en los niveles de colesterol en suero y el grosor de la íntima entre los grupos (p = 0.000). El resto de los grupos tenía más engrosamiento de la íntima que el grupo I (p = 0.000). El grupo III tenía una íntima más gruesa que los grupos IV y V (p = 0,009, p = 0.011 respectivamente). No hubo ninguna diferencia significativa entre los grupos en cuanto al espesor de la media (p = 0.432). CONCLUSIÓN: La infección y la dieta rica en colesterol tienen un efecto sinérgico sobre la aterosclerosis en las arterias pulmonares. Sin embargo, los antibióticos y los agentes antiinflamatorios podrían ser útiles para la prevención.