RESUMEN
Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control. The OVX/T1DM and OVX/T1DM+Zn groups had significantly higher serum alkaline phosphatase activity than the control. The supplemented group had higher levels of serum-ionized calcium and phosphorus than the nonsupplemented group. The RANKL/OPG ratio was similar between the control and OVX/T1DM+Zn groups, whereas it was higher in the OVX/T1DM group. In conclusion, Zn supplementation prevents bone alteration in chronic OVX/T1DM rats, as demonstrated by the reduced RANKL/OPG ratio and preservation of bone architecture. The findings may represent a novel therapeutic approach to preventing OVX/T1DM-induced bone alterations.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Suplementos Dietéticos , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Zinc/administración & dosificación , Fosfatasa Alcalina/sangre , Animales , Glucemia/metabolismo , Huesos/efectos de los fármacos , Calcio/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Osteoprotegerina/genética , Ovariectomía , Fósforo/sangre , Ligando RANK/genética , Ratas , Ratas WistarRESUMEN
Type 1 diabetes mellitus (T1DM) and estrogen deficiency are associated with several alterations in bone turnover. Zinc (Zn) is required for growth, development, and overall health. Zinc has been used in complementary therapy against bone loss in several diseases. We hypothesized that Zn supplementation represents a potential therapy against severe bone loss induced by the combined effect of estrogen deficiency and T1DM. We evaluated the protective effect of Zn against bone alterations in a chronic model of these disorders. Female Wistar rats were ramdomized into 3 groups (5 rats each): control, OVX/T1DM (ovariectomized rats with streptozotocin-induced T1DM), and OVX/T1DM+Zn (OVX/T1DM plus daily Zn supplementation). Serum biochemical, bone histomorphometric, and molecular analyses were performed. Histomorphometric parameters were similar between the control and OVX/T1DM+Zn groups, suggesting that Zn prevents bone architecture alterations. In contrast, the OVX/T1DM group showed significantly lower trabecular width and bone area as well as greater trabecular separation than the control...
Asunto(s)
Diabetes Mellitus , Ratas , ZincRESUMEN
PURPOSE: Considering that important scientific advances have been obtained through studies based on experimental Diabetes mellitus, and that tamoxifen action in humans remains unknown, the aim of the present work is to follow the modifications promoted by diabetes and tamoxifen in the electrophoretic profile of plasmatic proteins. METHODS: It was used 27 Wistar female rats (180-250 body weight), randomicaly divided into five groups: C1 (n = 3, received vehicle), C2 (n = 3, no treatment), T (n =5, treated with tamoxifen, 0.3mg/Kg/day), D (n = 8, experimental diabetes by estreptozotocin, 45mg/Kg and DT (n = 8, diabetic treated with tamoxifen). The electrophoresis was accomplished in cellulose acetate. pH 8.6-8.8, TECNOW chamber, and the strains were stained by Ponceau S. The total proteins were determined by the Biuret method (Labtest). Proteinograms were obtained in densitometer BioSystems BTS-235. RESULTS: Albumin decreased progressively in the groups T, D and DT; a1 fraction increased in groups T and DT; a2 fraction increased in groups T and D, including a synergic effect in group DT; a fraction increased in groups T and D; a fraction increased in groups T, D and DT. CONCLUSIONS: The results indicate an acute phase resposta, with synergic effect of tamoxifen and diabetes, suggesting a probable hepatic lesion.
Asunto(s)
Proteínas Sanguíneas/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Tipo 1/sangre , Antagonistas de Estrógenos/farmacología , Tamoxifeno/farmacología , Análisis de Varianza , Animales , Glucemia/efectos de los fármacos , Electroforesis de las Proteínas Sanguíneas , Peso Corporal/efectos de los fármacos , Ciclo Estral/efectos de los fármacos , Femenino , Ratas , Ratas WistarRESUMEN
Although osteopenia has been associated with human diabetes mellitus, the pathogenesis of diabetic osteopenia is unclear. In the present study, we evaluated the effect of diabetes on histomorphometry, bone mineral density (BMD)-measured by dual-energy X-ray absorptiometry (DXA)-and biomarkers of bone metabolism in rats up to 120 days after the onset of experimental diabetes. Female Wistar rats with a regular estrous cycle were randomly divided into two groups: control rats (n = 15) and diabetic rats without insulin treatment (n = 25). Diabetes was induced by injection of alloxan and was confirmed by the determination of blood glucose concentration (>250 mg/dl). The results revealed an approximate threefold increase of femoral trabecular distance in diabetic rats compared to controls. Conversely, trabecular thickness and bone trabecular volume were reduced twofold and 77%, respectively. BMD in both the metadiaphyseal region and total area of the femur was found to be clearly reduced in diabetic animals, with no significant differences between the groups. Serum alkaline phosphatase (ALP) and tartarate-resistant acid phosphatase (TRAP) activities showed significant six- and twofold increases, respectively, in diabetic rats. There were significant decreases in serum calcium and albumin concentrations in diabetic rats, but no difference was observed in serum magnesium, phosphorus, or creatinine concentrations between the groups. Overall, our findings support the conclusion that the diabetic state is associated with alterations in bone turnover, resulting in the development of osteopenia, which is related to the time of evolution of the disorder.
Asunto(s)
Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/patología , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Fosfatasa Ácida/sangre , Fosfatasa Alcalina/sangre , Animales , Biomarcadores/análisis , Biomarcadores/sangre , Glucemia/metabolismo , Densidad Ósea/fisiología , Enfermedades Óseas Metabólicas/metabolismo , Huesos/metabolismo , Huesos/patología , Calcio/sangre , Creatina/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Ciclo Estral , Femenino , Isoenzimas/sangre , Ratas , Ratas Wistar , Albúmina Sérica/análisis , Fosfatasa Ácida TartratorresistenteRESUMEN
OBJETIVO: Considerando-se que importantes avanços científicos têm sido obtidos através de estudos com Diabetes mellitus experimental, e que a ação do tamoxifeno em humanos permanece obscura, o presente trabalho objetiva acompanhar as modificações promovidas pelo diabetes e tamoxifeno no perfil eletroforético das proteínas plasmáticas. MÉTODOS: Foram utilizados 27 ratos fêmeas Wistar (180-220g peso corporal), divididos randomicamente em 5 grupos: C1 (n=3, receberam veículo), C2 (n=3, sem tratamento), T (n=5, tratados com tamoxifeno, 0,3mg/kg/dia), D (n=8, diabéticos experimentais por estreptozotocina, 45mg/Kg) e DT (n=8, diabéticos tratados com tamoxifeno). A eletroforese foi realizada em acetato de celulose, pH 8,6-8,8, cuba TECNOW, e as fitas foram coradas em Ponceau S. As proteínas totais foram determinadas pelo método do Biureto (Kit Labtest). Os proteinogramas foram obtidos em densitômetro BioSystems BTS-235. RESULTADOS: Albumina diminuiu progressivamente nos grupos T, D e DT; a fração a1 aumentou nos grupos T e DT; a fração a2 aumentou nos grupos T e D, havendo efeito aditivo no grupo DT; a fração b aumentou nos grupos T e D; a fração g aumentou nos grupos T, D e DT. CONCLUSÃO: Os resultados indicam uma resposta de fase aguda, com efeito aditivo do tamoxifeno e diabetes, sugerindo uma provável lesão hepática.