Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats / Tratamento com Resveratrol Normaliza a Função Endotelial e a Pressão Arterial em Ratas Ovariectomizadas

Abstract Background: Despite knowing that resveratrol has effects on blood vessels, blood pressure and that phytostrogens can also improve the endothelium-dependent relaxation/vasodilation, there are no reports of reveratrol's direct effect on the endothelial function and blood pressure of animals with estrogen deficit (mimicking post-menopausal increased blood pressure). Objective: To verify the effect of two different periods of preventive treatment with resveratrol on blood pressure and endothelial function in ovariectomized young adult rats. Methods: 3-month old female Wistar rats were used and distributed in 6 groups: intact groups with 60 or 90 days, ovariectomized groups with 60 or 90 days, and ovariectomized treated with resveratrol (10 mg/kg of body weight per day) for 60 or 90 days. The number of days in each group corresponds to the duration of the experimental period. Vascular reactivity study was performed in abdominal aortic rings, systolic blood pressure was measured and serum nitric oxide (NO) concentration was quantified. Results: Ovariectomy induced blood pressure increase 60 and 90 days after surgery, whereas the endothelial function decreased only 90 days after surgery, with no difference in NO concentration among the groups. Only longer treatment (90 days) with resveratrol was able to improve the endothelial function and normalize blood pressure. Conclusion: Our results suggest that 90 days of treatment with resveratrol is able to improve the endothelial function and decrease blood pressure in ovariectomized rats.

Resumo Fundamentos: Apesar de se saber que o resveratrol apresenta efeitos sobre a pressão arterial e os vasos sanguíneos, e que os fitoestrógenos podem melhorar o relaxamento/vasodilatação dependente do endotélio, não há relatos do efeito direto do resveratrol sobre a pressão arterial e a função endotelial em animais com deficiência de estrógeno (mimetizando a pressão arterial aumentada pós-menopausa). Objetivo: Verificar o efeito de dois diferentes períodos de tratamento preventivo com resveratrol sobre a pressão arterial e a função endotelial em ratas adultas jovens ovariectomizadas. Métodos: Foram utilizadas ratas Wistar com 3 meses de idade, distribuídas em 6 grupos: grupos intactas com 60 ou 90 dias, grupos ovariectomizadas com 60 ou 90 dias, grupos ovariectomizadas e tratadas com resveratrol na dose de 10mg/kg de massa corporal por dia, durante 60 ou 90 dias, sendo o número de dias em cada grupo relativo à duração do período experimental. Foi realizado um estudo de reatividade vascular em anéis da aorta abdominal, mensurada a pressão arterial sistólica e quantificada a concentração sérica de óxido nítrico (NO). Resultados: A ovariectomia induziu aumento da pressão arterial 60 e 90 dias após a cirurgia, enquanto a função endotelial decaiu apenas após 90 dias, e não houve diferença na concentração de NO entre os grupos. Apenas o tratamento prolongado com resveratrol (90 dias) foi capaz de melhorar a função endotelial e normalizar a pressão arterial. Conclusão: Nossos resultados sugerem que o tratamento por 90 dias com resveratrol é capaz de melhorar a função endotelial e diminuir a pressão sanguínea em ratas ovariectomizadas.

Effect of Resveratrol on periodontal pathogens during experimental periodontitis in rats

Abstract The objective of this study was to investigate the antibacterial effect of resveratrol against putative periodontal pathogens during the progression of experimental periodontitis in rats. Periodontitis was induced in rats in one of the first molars chosen to receive a ligature. Animals were assigned to one of two groups: daily administration of the placebo solution (control group, n = 12) or 10 mg/Kg of resveratrol (RESV group, n = 12). The therapies were administered systemically for 30 days, for 19 days before periodontitis induction and then for another 11 days. Then, the presence and concentrations of Porphyromonas gingivalis, Tannerella forsythia and Aggregatibacter actinomycetemcomitans in the cotton ligatures collected from the first molars were evaluated using real-time PCR. Inter-group comparisons of the microbiological outcomes revealed that no differences were detected for P. gingivalis, T. forsythia and A. actinomycetemcomitans levels (p > 0.05). Continuous use of resveratrol did not promote additional benefits in microbiological outcomes during experimental periodontitis in rats.

Resveratrol plays important role in protective mechanisms in renal disease - mini-review / Resveratrol desempenha importante papel no mecanismo de proteção na doença renal - mini-revisão

Resveratrol (RESV) is a polyphenolic compound found in various plants, including grapes, berries and peanuts, and its processed foods as red wine. RESV possesses a variety of bioactivities, including antioxidant, anti-inflammatory, cardioprotective, antidiabetic, anticancer, chemopreventive, neuroprotective, renal lipotoxicity preventative, and renal protective effects. Numerous studies have demonstrated that polyphenols promote cardiovascular health. Furthermore, RESV can ameliorate several types of renal injury in animal models, including diabetic nephropathy, hyperuricemic, drug-induced injury, aldosterone-induced injury, ischemia-reperfusion injury, sepsis-related injury, and endothelial dysfunction. In addition, RESV can prevent the increase in vasoconstrictors, such as angiotensin II (AII) and endothelin-1 (ET-1), as well as intracellular calcium, in mesangial cells. Together, these findings suggest a potential role for RESV as a supplemental therapy for the prevention of renal injury.

Resveratrol (RESV) é um composto fenólico encontrado em várias plantas, como a uva e amendoim, e seus produtos derivados, como o vinho tinto. RESV possui uma variedade de bioatividades, incluindo antioxidantes, anti-inflamatória, cardioprotetoras, antidiabetes, anticancerígeno, quimiopreventivo, neuroprotetor, lipotoxicidade renal, e efeitos protetores renais. Numerosos estudos demonstraram que os polifenois promovem a saúde cardiovascular e podem reparar vários tipos de lesões renais em modelos animais, incluindo a nefropatia diabética, hiperuricemia, lesão induzida por droga, lesão induzida pela aldosterona, lesão de isquemia-reperfusão, lesões relacionadas com sepsis, e disfunção endotelial. Além disso, RESV pode prevenir o aumento de vasoconstritores, tais como angiotensina II (AII) e endotelina-1 (ET-1), bem como o cálcio intracelular, em células mesangiais. Em conjunto, estes resultados sugerem um importante papel para o RESV como uma terapia complementar na prevenção de lesões renais.

Propuesta de reformas a los prestadores públicos de servicios médicos en Chile: “fortaleciendo la opción pública” / A reform proposal to strengthen public health care

Currently, there is no discussion on the need to improve and strengthen the institutional health care modality of FONASA (MAI), the health care system used by the public services net and by most of the population, despite the widely known and long lasting problems such as waiting lists, hospital debt with suppliers, lack of specialists and increasing services purchase transference to the private sector, etc. In a dichotomous sectorial context, such as the one of health’s social security in Chile (the state on one side and the market on the other), points of view are polarized and stances tend to seek refuge within themselves. As a consequence, to protect the public solution is commonly associated with protecting the “status quo”, creating an environment that is reluctant to change. The author proposes a solution based on three basic core ideas, which, if proven effective, can strengthen each other if combined properly. These are: network financing management, governance of health care services in MAI and investments and human resources in networked self-managed institutions. The proposal of these core ideas was done introducing a reality testing that minimizes the politic complexity of their implementation.

Use of microRNAs in directing therapy and evaluating treatment response in colorectal cancer / Utilização dos microRNAs no direcionamento da terapia e na avaliação da resposta ao tratamento do câncer colorretal

Colorectal cancer is the third most common cancer worldwide. Survival and prognosis depend on tumor stage upon diagnosis, and in more than 50% of cases, the tumor has already invaded adjacent tissues or metastasis has occurred. Aiming to improve diagnosis, clinical prognosis and treatment of patients with colorectal cancer, several studies have investigated microRNAs as molecular markers of the disease due to their potential regulatory functions on tumor suppressor genes and oncogenes. This review aimed to summarize the main topics related to the use of microRNAs in diagnosis, clinical prognosis and evaluating treatment response in colorectal cancer.

O câncer colorretal é o terceiro tipo de câncer mais comum em todo o mundo. A sobrevivência e o prognóstico dependem do estágio do tumor no diagnóstico, momento em que, em mais de 50% dos casos, o tumor já invadiu tecidos adjacentes ou ocorreu metástase. Objetivando-se melhorar o diagnóstico, o prognóstico clínico e o tratamento de pacientes com câncer colorretal, vários estudos investigaram microRNAs como marcadores moleculares da doença, devido à sua função reguladora potencial sobre genes supressores de tumor e oncogenes. Esta revisão procura resumir os principais tópicos relacionados ao uso de microRNAs no diagnóstico, na determinação do prognóstico clínico e na avaliação de resposta ao tratamento do câncer colorretal.

The qualitative effects of resveratrol and coenzyme Q10 administration on the gluteus complex muscle morphology of SJL/J mice with dysferlinopathy / Efectos cualitativos de la administración de resveratrol y coenzima Q10 en la morfología del complejo muscular glúteo de ratones SJL/J con disferlinopatía

Dysferlinopathy is a form of muscular dystrophy affecting muscles of the shoulder and pelvic girdles, resulting from inheritance of a mutated dysferlin gene. The encoded dysferlin protein is proposed to be involved in sarcolemmal vesicle fusion with a disrupted plasma membrane; however, with defective protein function these vesicles accumulate beneath the disruption site but are unable to fuse with it and reseal the membrane, thus rendering the membrane repair mechanism defective. The SJL/J mouse model presents with characteristics much like the commonest human condition. Immune modulators have long been under study in the maintenance of muscle health in muscular dystrophies. Such supplementary treatment would ideally suppress inflammation, preventing the immune response toward degenerating muscle from causing additional muscle fiber death, and thus provide a mechanism by which to prolong the life of muscle fibers with inherently defective healing apparatus. For this purpose the anti-inflammatory supplement resveratrol and the membrane-protective supplement coenzyme Q10 were administered separately and in combination to experimental animals to determine their effectiveness in possible therapy of dysferlinopathy. The findings of this study report that low doses of resveratrol and coenzyme Q10 supplementation in exclusivity were unable to afford much protection to muscle fibers at the tissue level. High doses of coenzyme Q10 proved more effective in reducing attenuating inflammation; and combination treatment with resveratrol and coenzyme Q10 provided not only the membrane-protective effects of coenzyme Q10, but also the anti-inflammatory effects of resveratrol which failed to materialize at sufficient levels in exclusive administration.

Disferlinopatía es una forma de distrofia muscular que afecta a los músculos de los hombros y cintura pélvica, resultado de la herencia y mutación del gen de la distrofina. Sugerimos que la proteína codificada distrofina que integra la estructura sarcolemal con una membrana plasmática interrumpida, que al presentar una proteína defectuosa, las estructuras se acumulan debajo del sitio de alteración sin lograr fundirse con éste y cerrar la membrana afectando el mecanismo de reparación. El modelo de ratón SJL / J se presenta con características muy similares a una condición humana común. Los inmunomoduladores han sido objeto de estudio en el mantenimiento de la salud muscular en las distrofias musculares. Este tipo de tratamiento suplementario puede ser ideal para suprimir la inflamación, en la prevención de la respuesta inmune en la degeneración muscular causando la muerte adicional de fibra muscular, y al mismo tiempo proporcionar, un mecanismo con el cual prolongar la vida útil de aquellas fibras musculares con el aparato de sanación comprometido. Para ello, el Resveratrol suplemento anti-inflamatorio y el suplemento protector de membrana coenzima Q10 se administró por separado y en combinación en los animales de laboratorio para determinar su efectividad en el tratamiento de posible disferlinopatía. Los resultados de este estudio indican que el Resveratrol en menor dosis y la coenzima Q 10 administrados como suplementos de manera exclusiva, no demostraron efectos de protección de las fibras musculares a nivel del tejido. Una alta dosis de coenzima Q10 demostró ser más efectiva en la reducción de la inflamación; adicionalmente, el tratamiento combinado de Resveratrol y coenzima Q10 proporcionó efectos protectores de membrana, además de los efectos anti-inflamatorios del Resveratrol cuyo nivel no alcanzó la efectividad suficiente al ser administrado en forma exclusiva.

Antioxidantes / Antioxidants

Nuestra piel está constantemente expuesta al estrés oxidativo endógeno y exógeno, el cual juega un papel fundamental tanto en el envejecimiento intrínseco como extrínseco. El estrés oxidativo se debe a la producción de especies reactivas de oxígeno, también conocidas como radicales libres. Las estructuras vitales que se ven afectadas por este proceso son el ADN, elementos del citoesqueleto, proteínas celulares y membranas celulares. El cuerpo posee mecanismos de defensa contra los radicales libres, denominados antioxidantes, los cuales son capaces de reducirlos y neutralizarlos. Sin embargo, como parte natural del proceso de envejecimiento, no sólo la producción de especies reactivas de oxígeno aumenta, sino que los mecanismos endógenos de defensa disminuyen, resultando en un desbalance con predominio de radicales libres no neutralizados que dañan las estructuras del organismo. Aunque el cuerpo posee antioxidantes endógenos y ciertos alimentos son ricos en antioxidantes, muchos creen que niveles más altos de estas sustancias pueden obtenerse con suplementos alimentarios. En consecuencia, ha llegado a ser muy popular el uso de antioxidantes en suplementos orales o en forma tópica, los cuales podrían potencialmente aminorar los efectos adversos de las especies reactivas de oxígeno. En esta revisión se analizan los antioxidantes más conocidos que se encuentran incorporados en los productos cosméticos o que son administrados por vía oral en los pacientes interesados en la cosmética personal.

Our skin is constantly exposed to endogenous and exogenous oxidative stress, which plays a pivotal role in intrinsic and extrinsic aging. Oxidative stress is delivered by the creation of reactive oxygen species also known as free radicals. Vital structures that can be adversely affected by this process are DNA, cytoskeletal elements, cellular proteins, and cellular membranes. The body possesses defense mechanisms against free radicals, which are called antioxidants, and are able to reduce and neutralize them. However, as part of the natural aging process, not only does the production of reactive oxygen species increase, but our endogenous defense mechanisms decrease resulting in an imbalance and increased number of unchecked free radicals damaging vital structures of the body. Although the body possesses endogenous antioxidants and certain foods are rich in antioxidants, many believe that higher levels can be achieved by supplementation. Consequently, the use of antioxidants as oral supplements or topical formulation should be able to lessen the harmful adverse effects induced by reactive oxygen species and has thus become popular. This review discusses the most popular types of antioxidants found in cosmetic products or taken orally by cosmetic patients.

Suppression of prostate cancer growth by resveratrol in the transgenic rat for adenocarcinoma of prostate (TRAP) model.

Research into actions of resveratrol, abundantly present in red grape skin, has been greatly stimulated by its reported beneficial health influence. Since it was recently proposed as a potential prostate cancer chemopreventive agent, we here performed an in vivo experiment to explore its effect in the Transgenic Rat for Adenocarcinoma of Prostate (TRAP) model, featuring the rat probasin promoter/SV 40 T antigen. Resveratrol suppressed prostate cancer growth and induction of apoptosis through androgen receptor (AR) down-regulation, without any sign of toxicity. Resveratrol not only downregulated androgen receptor (AR) expression but also suppressed the androgen responsive glandular kallikrein 11 (Gk11), known to be an ortholog of the human prostate specific antigen (PSA), at the mRNA level. The data provide a mechanistic basis for resveratrol chemopreventive efficacy against prostate cancer.

Effect of alpha lipoic acid, melatonin and trans resveratrol on intracerebroventricular streptozotocin induced spatial memory deficit in rats.

In the present study, the effect of antioxidants-alpha lipoic acid, melatonin and trans resveratrol were studied against intracerebroventricular streptozotocin induced spatial memory deficit. Male Wistar rats were injected with intracerebroventricular streptozotocin bilaterally. The rats were treated chronically with alpha lipoic acid (200 mg/kg, po), melatonin (20 mg/kg, ip) and trans resveratrol (20 mg/kg, ip) for 18 days starting from day 1 of streptozotocin injection in separate groups. The spatial memory was evaluated using the Morris water maze task. The intracerebroventricular streptozotocin rats treated with antioxidants showed significantly less spatial memory deficit both in the acquisition and probe trials as compared to the vehicle treated rats. The study demonstrated the effectiveness of alpha lipoic acid, melatonin and trans resveratrol in preventing spatial memory deficit induced by intracerebroventricular streptozotocin and it's potential in age related neurodegenerative disorders where oxidative stress is involved such as Alzheimer's disease.