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1.
Food Funct ; 9(9): 4791-4801, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30128468

RESUMO

Milk contains various bioactive components with osteoanabolic properties. This study investigates the comparative effect of the whey-derived antioxidative (YVEEL) and angiotensin-converting enzyme inhibitory (YLLF) bioactive peptides on bone remodelling in ovariectomised (OVX) osteoporotic rat model. OVX animals were administered with antioxidative (AO) (500 µg kg-1 day-1) and angiotensin-converting enzyme inhibitory (ACE inhibitory) (50 µg kg-1 day-1) peptides for eight weeks. Trabecular microarchitectural parameters of femoral and tibiae bone were determined using micro-CT scan. Bone formation, resorption, turnover markers (ALP, RANKL, OCN) and inflammatory cytokines (TNF-α, TGF-ß, IFN-γ) were determined by ELISA. Both AO and ACE inhibitory peptides inhibited the increase in bone turnover and inflammatory cytokines while increased the bone formation markers. The altered morphometric parameters of femoral and tibiae bones due to OVX were strikingly attenuated by the peptide administration. The results indicated that AO peptide exerts more osteoprotective potential than ACE inhibitory peptide by suppressing inflammatory status and enhancing bone formation markers.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Suplementos Nutricionais , Oligopeptídeos/uso terapêutico , Osteoporose Pós-Menopausa/prevenção & controle , Fragmentos de Peptídeos/uso terapêutico , Proteínas do Soro do Leite/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides , Antioxidantes/química , Antioxidantes/uso terapêutico , Biomarcadores/sangue , Conservadores da Densidade Óssea/química , Remodelação Óssea , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/imunologia , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/imunologia , Feminino , Humanos , Mediadores da Inflamação/sangue , Oligopeptídeos/química , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/imunologia , Ovariectomia/efeitos adversos , Fragmentos de Peptídeos/química , Distribuição Aleatória , Ratos Wistar , Tomografia Computadorizada por Raios X , Proteínas do Soro do Leite/química
2.
Br J Nutr ; 111(5): 836-46, 2014 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-24073920

RESUMO

Resveratrol (Res), a polyphenol that is abundant in many medicinal plants and is a selective oestrogen receptor modulator, exhibits multiple biological activities. In the present study, we determined whether Res prevents oestrogen deficiency-induced osteopenia and whether Res administration decreases pathological changes in the endometrium and lumen of the uterus compared with oestradiol replacement therapy (ERT). A total of sixty 3-4-month-old female Wistar rats were randomly divided into a sham-operated group (Sham) and five ovariectomy (OVX) subgroups, i.e. OVX rats as a control group (OVX); OVX rats receiving oestradiol valerate (ERT, 0·8 mg/kg); and OVX rats receiving Res 20, 40 and 80 mg/kg. Daily oral administration was initiated at week 2 after OVX for 12 weeks. A dose-response difference was observed in the effects of Res on bone mineral density (BMD) and trabecular microarchitecture. Only at the highest dose, bone loss was almost equivalent to that observed in the ERT group. The dose-response effects of Res on the biochemical parameters (alkaline phosphatase, IL-6, TNF-α and transforming growth factor-ß1 concentrations in the serum as well as urinary Ca and P excretion) and the expressions of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL:osteoprotegerin protein ratio in the femur were also observed. Furthermore, the thickening of the endometrium and the infiltration of lymphocytes were prevented in all the three Res-treated groups compared with the ERT group. In conclusion, Res treatment not only improves BMD and trabecular microarchitecture but also does not affect the uterus and Res might be a potential remedy for the treatment of postmenopausal osteoporosis.


Assuntos
Antioxidantes/uso terapêutico , Suplementos Nutricionais , Hiperplasia Endometrial/prevenção & controle , Endométrio/patologia , Osteoporose Pós-Menopausa/prevenção & controle , Fitoestrógenos/uso terapêutico , Estilbenos/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Densidade Óssea , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Suplementos Nutricionais/efeitos adversos , Modelos Animais de Doenças , Hiperplasia Endometrial/induzido quimicamente , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Fêmur/química , Fêmur/imunologia , Fêmur/metabolismo , Fêmur/patologia , Humanos , Osteoporose Pós-Menopausa/imunologia , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Osteoprotegerina/metabolismo , Fitoestrógenos/administração & dosagem , Fitoestrógenos/efeitos adversos , Ligante RANK/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Resveratrol , Estilbenos/administração & dosagem , Estilbenos/efeitos adversos , Fatores de Tempo
4.
Clin Ther ; 34(3): 521-36, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22440513

RESUMO

BACKGROUND: Postmenopausal osteoporosis results from bone loss and decreased bone strength mediated by an increased rate of bone remodeling secondary to reduced estrogen levels. Remodeling cycles are initiated by osteoclasts, the formation, function, and survival of which depend on RANK ligand (RANKL). RANKL inhibition therefore represents a novel strategy for reducing remodeling and its effects on fracture risk. OBJECTIVES: The goal of this study was to review the preclinical and clinical evidence supporting the value of RANKL inhibition in conditions of bone loss and to provide the rationale for the use of the fully human antibody denosumab, a RANKL inhibitor, in such conditions. METHODS: We searched PubMed from January 2005 to May 2011 using the following terms: RANK Ligand, RANKL, denosumab, and NOT cancer, metastatic bone, or rheumatoid in the title. RESULTS: The search method retrieved 111 articles. Preclinical evidence from several bone disease models suggests that RANKL inhibition leads to increased bone volume, density, and strength. Denosumab prevents RANKL from binding to its receptor, decreasing osteoclast activity and thereby reducing bone resorption and increasing cortical and trabecular bone mass and strength. It has consistently been reported to reduce bone turnover, increase bone density, and reduce the risk of fracture in clinical studies of postmenopausal women. Phase III head-to-head trials comparing denosumab with the bisphosphonate alendronate reported that denosumab was associated with significantly greater increases in bone density. Eczema as an adverse event and cellulitis as a serious adverse event were more common with denosumab than with placebo. CONCLUSIONS: Preclinical studies defined the role of RANKL in bone remodeling and provided evidence for the therapeutic potential of RANKL inhibition in conditions of bone loss. Clinical studies evaluating RANKL inhibition with denosumab in postmenopausal women have reported significant reductions in vertebral, nonvertebral, and hip fractures, providing evidence compatible with the use of denosumab in postmenopausal women with osteoporosis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Osso e Ossos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Ligante RANK/antagonistas & inibidores , Animais , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Ensaios Clínicos como Assunto , Denosumab , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Estrogênios/deficiência , Feminino , Humanos , Osteoporose/imunologia , Osteoporose/metabolismo , Osteoporose/patologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/imunologia , Osteoporose Pós-Menopausa/metabolismo , Osteoporose Pós-Menopausa/patologia , Testosterona/deficiência , Resultado do Tratamento
6.
Cell Mol Immunol ; 3(1): 41-5, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16549048

RESUMO

The plasma level of dehydroepiandrosterone (DHEA) decreases gradually along with aging. The beneficial effects of DHEA as an anti-aging steroid, such as the stimulatory effect on immune system, anti-diabetes mellitus, anti-atherosclerosis, anti-dementia, anti-obesity and anti-osteoporosis have been demonstrated in experiment both in vitro and in vivo. It is important to investigate the effective mechanism of DHEA in therapeutics for postmenopausal osteoporosis. Having isolated and cultured osteoblasts (OBs) and osteoclasts (OCs), we analysed the effect of DHEA on osteoblastic viability, regulation of DHEA on the expression of osteoprotegerin (OPG)/receptor activator of NF-kappaB ligand (RANKL) mRNA in OBs, and then observed the action of DHEA on bone resorption of OCs in the presence or absence of OBs. The results showed that DHEA improved viability of OBs within the concentration range of 0.01-1 microM, especially at the concentration of 0.1 microM. DHEA could apparently increase the ratio of OPG/RANKL mRNA in OBs. In the presence of OBs, DHEA could decrease the number and area of absorption lacuna of specula. We concluded, therefore, only in the presence of OBs, DHEA could inhibit the bone resorption of OCs, which may be mediated by OPG/RANKL of OBs.


Assuntos
Adjuvantes Imunológicos/farmacologia , Reabsorção Óssea/metabolismo , Proteínas de Transporte/biossíntese , Desidroepiandrosterona/farmacologia , Glicoproteínas de Membrana/biossíntese , Regulação para Cima/efeitos dos fármacos , Adjuvantes Imunológicos/uso terapêutico , Animais , Animais Recém-Nascidos , Reabsorção Óssea/imunologia , Células Cultivadas , Desidroepiandrosterona/uso terapêutico , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Técnicas de Cultura de Órgãos , Osteoblastos/citologia , Osteoblastos/imunologia , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteoclastos/imunologia , Osteoclastos/metabolismo , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/imunologia , Osteoporose Pós-Menopausa/metabolismo , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Regulação para Cima/imunologia
8.
Horm Metab Res ; 27(1): 31-4, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7729790

RESUMO

Calcitonin pharmacokinetics and pharmacodynamics were studied in two groups of patients with postmenopausal osteoporosis, who, treated for one year with intranasal Asu1.7-eel calcitonin (eCT), had (Ab+) and had not (Ab-) developed a specific immune response to the drug. The treatment consisted of daily intranasal administrations of eCT (80 IU/die) with 1 g supplemental calcium. Eight women who had developed specific antibodies and 5 who had not, were given 50 IU of CT i.m., in order to assess the pharmacokinetics and pharmacodynamics of the drug. The rise of serum levels of the hormone was significantly greater in Ab+ than in Ab- patients. At the end of the study, no significant differences in mineral bone loss between the two groups were found. In conclusion, the presence of antibodies to eCT does not represent a negative event in the therapy of osteoporosis, but significantly affects the pharmacokinetics of the drug.


Assuntos
Anticorpos/fisiologia , Calcitonina/imunologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Anticorpos/sangue , Calcitonina/farmacocinética , Calcitonina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/imunologia
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