Resveratrol Treatment Normalizes the Endothelial Function and Blood Pressure in Ovariectomized Rats.

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. 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.

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.

Exercise alters myostatin protein expression in sedentary and exercised streptozotocin-diabetic rats

Objective The aim of this study was to analyze the effect of exercise on the pattern of muscle myostatin (MSTN) protein expression in two important metabolic disorders, i.e., obesity and diabetes mellitus. Materials and methods MSTN, is a negative regulator of skeletal muscle mass. We evaluated the effect of exercise on MSTN protein expression in diabetes mellitus and high fat diet-induced obesity. MSTN protein expression in gastrocnemius muscle was analyzed by Western Blot. P < 0.05 was assumed. Exercise induced a significant decrease in glycemia in both diabetic and obese animals. Results The expression of precursor and processed protein forms of MSTN and the weight of gastrocnemius muscle did not vary in sedentary or exercised obese animals. Diabetes reduced gastrocnemius muscle weight in sedentary animals. However, gastrocnemius muscle weight increased in diabetic exercised animals. Both the precursor and processed forms of muscle MSTN protein were significantly higher in sedentary diabetic rats than in control rats. The precursor form was significantly lower in diabetic exercised animals than in diabetic sedentary animals. However, the processed form did not change. Conclusion These results demonstrate that exercise can modulate the muscle expression of MSTN protein in diabetic rats and suggest that MSTN may be involved in energy homeostasis. .

Modifications in bone matrix of estrogen-deficient rats treated with intermittent PTH.

Bone matrix dictates strength, elasticity, and stiffness to the bone. Intermittent parathyroid hormone (iPTH), a bone-forming treatment, is widely used as a therapy for osteoporosis. We investigate whether low doses of intermittent PTH (1-34) change the profile of organic components in the bone matrix after 30 days of treatment. Forty 6-month-old female Wistar rats underwent ovariectomy and after 3 months received low doses of iPTH administered for 30 days: daily at 0.3 µg/kg/day (PTH03) or 5 µg/kg/day (PTH5); or 3 times per week at 0.25 µg/kg/day (PTH025). After euthanasia, distal femora were processed for bone histomorphometry, histochemistry for collagen and glycosaminoglycans, biochemical quantification of sulfated glycosaminoglycans, and hyaluronan by ELISA and TUNEL staining. Whole tibiae were used to estimate the bone mineral density (BMD). Histomorphometric analysis showed that PTH5 increased cancellous bone volume by 6% over vehicle-treated rats. In addition, PTH5 and PTH03 increased cortical thickness by 21% and 20%, respectively. Tibial BMD increased in PTH5-treated rats and this group exhibited lower levels of chondroitin sulfate; on the other hand, hyaluronan expression was increased. Hormonal administration in the PTH5 group led to decreased collagen maturity. Further, TUNEL-positive osteocytes were decreased in the cortical compartment of PTH5 whereas administration of PTH025 increased the osteocyte death. Our findings suggest that daily injections of PTH at low doses alter the pattern of organic components from the bone matrix, favoring the increase of bone mass.

Effects of the long-term administration of alendronate on the mechanical properties of the basal bone and on osseointegration.

OBJECTIVE: To evaluate the effect of the long-term administration of alendronate on the mechanical properties of the basal bone and on osseointegration. MATERIAL AND METHODS: One hundred and sixty female rats were randomly allocated into two equally sized groups: the control (CTL) group, which received the subcutaneous administration of saline solution, and the alendronate (ALD) group, which received the subcutaneous administration of alendronate (1 mg/kg/week). After 120 days of these therapies, one implant was placed in each rat tibia. Ten animals in each group were euthanized at 5, 10, 15, 20, 25, 30, 45, or 60 days after surgery. The tibias with implants evaluated regarding the removal torque, bone-implant contact (BIC), the bone area fraction occupancy (BAFO), and Ca/P ratio. The femurs were evaluated regarding bone mineral density (BMD) and using mechanical tests to evaluate the maximal force of fracture, stiffness, and tenacity. RESULTS: The ALD group presented statistically significant higher BMD (all periods except 15 days), maximal force of fracture (at 20, 30, and 45 days), tenacity (at 10, 20, 30, and 45 days), stiffness (45 days), removal torque (at 20, 25 and 30 days), BIC (at 20 and 60 days), and BAFO (at 20, 30, and 45 days) than the CTL group. No differences were found between the groups regarding the Ca/P ratio. CONCLUSION: Previous long-term therapy with alendronate caused an increase in the BMD, maximal force of fracture of the bone without changing the inorganic composition and elastic deformability of this tissue. Furthermore, the ALD therapy enhanced osseointegration.

Comparação dos efeitos do laser de baixa potência e do ultrassom de baixa intensidade associado ao Biosilicato® no processo de reparo ósseo em tíbias de ratos / Comparative study of the effects of low-level laser and low-intensity ultrasound associated with Biosilicate® on the process of bone repair in the rat tibia

OBJETIVO: Verificar os efeitos da associação do Biosilicato® com o US e com o LLLT no processo de consolidação óssea em ratos, a partir da análise biomecânica e histológica. MÉTODOS: Foram utilizados 40 ratos machos distribuídos em quatro grupos (n = 10): grupo controle fratura sem tratamento (GCF); grupo tratado com Biosilicato® (GB); grupo tratado com Biosilicato® + laser (GBL); grupo tratado com Biosilicato® + US (GBUS). RESULTADOS: A análise biomecânica não apresentou diferença estatisticamente significativa nos grupos após o período experimental de 14 dias. Na análise morfométrica, o grupo controle apresentou presença moderada de tecido ósseo neoformado no interior dos defeitos e o grupo tratado com Biosilicato® apresentou resultados semelhantes. No entanto, foi observado o potencial osteogênico do biomaterial, uma vez que houve grande presença de células e tecido ósseo ao redor das partículas. Interessantemente, os grupos Biosilicato® associado ao laser terapêutico e ao US demonstraram quantidades menores de deposição de tecido ósseo quando comparados aos grupos controle fratura e Biosilicato®. CONCLUSÃO: A partir dos dados deste estudo podemos concluir que o Biosilicato® foi capaz de acelerar e potencializar a recuperação óssea, através da modulação do processo inflamatório e da estimulação da formação de tecido ósseo novo. No entanto, quando a LLLT ou o US foram associados, não foram encontrados resultados positivos.

OBJECTIVE: Verify the effects of the association between Biosilicate® and ultrasound and, Biosilicate® and laser in bone consolidation process of rats, through the biomechanical and histological analysis. METHODS: Forthy male rats were used. The animals were randomized into four groups (n=10): control group fracture no treated (CGF); group treated with Biosilicate® (BG); group treated with Biosilicate® and laser (BLG); group treated with Biosilicate® and ultrasound (BUG). RESULTS: The biomechanical analysis showed no significant difference among any groups after 14 days post-surgery. In the morphometric analysis, the control group showed moderate presence of new formed bone tissue inside the defects areas and the Biosilicate® group showed similar results. Despite those facts, the biomaterial osteogenic potential was demonstrated by the great amount of cells and bone tissue around the particles. Curiously, the Biosilicate® plus laser or ultrasound groups showed lower amounts of bone tissue deposition when compared with control fracture and Biosilicate® groups. CONCLUSION: The data from this study can conclude that Biosilicate® was able to accelerate and optimized the bone consolidation, through the modulation of the inflammatory process and the stimulation of new bone formation. However, when resources were associated, there are no positive results.

COMPARATIVE STUDY OF THE EFFECTS OF LOW-LEVEL LASER AND LOW-INTENSITY ULTRASOUND ASSOCIATED WITH BIOSILICATE(®) ON THE PROCESS OF BONE REPAIR IN THE RAT TIBIA.

OBJECTIVE: Verify the effects of the association between Biosilicate® and ultrasound and, Biosilicate® and laser in bone consolidation process of rats, through the biomechanical and histological analysis. METHODS: Forthy male rats were used. The animals were randomized into four groups (n=10): control group fracture no treated (CGF); group treated with Biosilicate® (BG); group treated with Biosilicate® and laser (BLG); group treated with Biosilicate® and ultrasound (BUG). RESULTS: The biomechanical analysis showed no significant difference among any groups after 14 days post-surgery. In the morphometric analysis, the control group showed moderate presence of new formed bone tissue inside the defects areas and the Biosilicate® group showed similar results. Despite those facts, the biomaterial osteogenic potential was demonstrated by the great amount of cells and bone tissue around the particles. Curiously, the Biosilicate® plus laser or ultrasound groups showed lower amounts of bone tissue deposition when compared with control fracture and Biosilicate® groups. CONCLUSION: The data from this study can conclude that Biosilicate® was able to accelerate and optimized the bone consolidation, through the modulation of the inflammatory process and the stimulation of new bone formation. However, when resources were associated, there are no positive results.

Low-level laser therapy, at 60 J/cm2 associated with a Biosilicate(®) increase in bone deposition and indentation biomechanical properties of callus in osteopenic rats.

We investigate the effects of a novel bioactive material (Biosilicate(®)) and low-level laser therapy (LLLT), at 60 J/cm(2), on bone-fracture consolidation in osteoporotic rats. Forty female Wistar rats are submitted to the ovariectomy, to induce osteopenia. Eight weeks after the ovariectomy, the animals are randomly divided into four groups, with 10 animals each: bone defect control group; bone defect filled with Biosilicate group; bone defect irradiated with laser at 60 J/cm(2) group; bone defect filled with Biosilicate and irradiated with LLLT, at 60 J/cm(2) group. Laser irradiation is initiated immediately after surgery and performed every 48 h for 14 days. Histopathological analysis points out that bone defects are predominantly filled with the biomaterial in specimens treated with Biosilicate. In the 60-J/cm(2) laser plus Biosilicate group, the biomaterial fills all bone defects, which also contained woven bone and granulation tissue. Also, the biomechanical properties are increased in the animals treated with Biosilicate associated to lasertherapy. Our results indicate that laser therapy improves bone repair process in contact with Biosilicate as a result of increasing bone formation as well as indentation biomechanical properties.

Some aspects of the pineal gland function

Rhythmic production of melatonin by the mammalian pineal gland occurs in response to noradrenergic stimulation which produces a cascade of biochemical events within the pinealocyte. Melatonin is involved in a wide range of physiological processes, including seasonal reproduction and diurnal activity rhythms. It was recently discovered that melatonin is a very potent hydroxyl radical scavenger, reinforcing its relationship with the aging process and the immune system.