RESUMO
All-trans retinoic acid (ATRA) has been extensively studied as an integrating component of endocrine functions in the pancreas. The aim of this study was to evaluate the effects of ATRA on physiopathological biomarkers in an experimental model of rat with type 1 diabetes induced by alloxan (T1D). Twenty Wistar rats were divided equally into five groups, each receiving a different treatment: a control group (CG), a diabetic group without T1D treatment, a diabetic group treated with ATRA, a diabetic group supplemented with vitamin E (VIT E), and a group that was given olive oil (V). The administration of ATRA for 17 days produced a significant reduction in weight and glucose levels, compared to the T1D and VIT E groups. The evaluation of total antioxidant capacity (TAC) and lipoperoxidation showed no relevant difference among the groups. The results of the histological analysis showed similarities both in the size and in the number of islets of Langerhans in the pancreatic tissue obtained from the ATRA group and the CG. ATRA displayed a significant reduction of glycemic values in diabetic rats. Ultrastructurally, ß-cells, acinar, and ductal cells restored their normal appearance. ATRA can contribute to the recovery of pancreatic damage due to alloxan induction. It seems that the antioxidant effect of ATRA is not responsible for the differences observed.
Assuntos
Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Pâncreas/efeitos dos fármacos , Tretinoína/farmacologia , Aloxano/metabolismo , Animais , Antioxidantes/metabolismo , Glicemia/efeitos dos fármacos , Feminino , Índice Glicêmico/efeitos dos fármacos , Pâncreas/metabolismo , Ratos , Ratos Wistar , Vitamina E/farmacologiaRESUMO
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.
Assuntos
Densidade Óssea/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Suplementos Nutricionais , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Zinco/administração & dosagem , Fosfatase Alcalina/sangue , Animais , Glicemia/metabolismo , Osso e Ossos/efeitos dos fármacos , Cálcio/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Osteoprotegerina/genética , Ovariectomia , Fósforo/sangue , Ligante RANK/genética , Ratos , Ratos WistarRESUMO
OBJECTIVE: To investigate the vitreous level of vascular endothelial growth factor (VEGF) and kinase insert domain-containing receptor (KDR) in diabetic rats, and to explore the role of VEGF and KDR in diabetic retinopathy. METHODS: Eighty-four adult Wistar rats were randomly divided into two groups. Fifty-eight rats in group A were injected intraperitoneally with streptozotocin to induce diabetes and 20 rats in group B were injected with physiological saline. Blood glucose meter was used to detect the blood glucose level at 72 hours after injection; blood glucose level >16.67 mmol/L was considered to be successful modelling. Blood glucose level was assayed and body mass was measured on the same modelling day, one week, two weeks and four weeks after modelling. Four weeks after modelling, the vitreous was taken and the VEGF and KDR levels were detected by enzyme-linked immunosorbent assay (ELISA). The eyeballs were fixed with paraform and embedded by petrolin for haematoxylin and eosin (H & E) staining. RESULTS: Forty-two rats survived and 16 rats died in group A. No rats died in group B. The blood glucose at one week, two weeks and four weeks between the two groups had statistical differences (p < 0.05). The weight at one week and two weeks between the two groups was not different but there was statistical difference at four weeks between the two groups (p < 0.01). The ELISA results showed that the VEGF and KDR levels were 0.276 ± 0.026 ng/mL and 2.936 ± 0.295 ng/mL in group A, 0.231 ± 0.021 ng/mL and 2.394 ± 0.227 ng/mL in group B, respectively. The VEGF and KDR levels of group A were higher than those of group B (p < 0.05). CONCLUSIONS: The changes of VEGF and KDR levels in the vitreous of diabetic rats were related to the early retinopathy induced by diabetes.
OBJETIVO: Investigar el nivel vítreo del factor de crecimiento endotelial vascular (FCEV) y receptor con dominio inserto-quinasa (KDR) en ratas diabéticas, y explorar el papel de FCEV y KDR en la retinopatía diabética. MÉTODOS: Ochenta y cuatro ratas adultas Wistar fueron divididas aleatoriamente en dos grupos. A cincuenta y ocho ratas en el grupo A se les inyectó estreptozotocinapor vía intraperitonealpara inducir diabetes, mientras que a 20 ratas en el grupo B se les inyectó una solución salina fisiológica. Se usó un medidor de glucosa en sangre para detectar el nivel de glucosa en sangre a las 72 horas después de la inyección. Un nivel de glucosa en sangre > 16.67 mmol/L se consideró como un modelo exitoso. Se analizó el nivel de glucosa en sangre, y se midió la masa corporal en el mismo día del modelado, y una semana, dos semanas, y cuatro semanas después del modelado. Cuatro semanas después del modelado, se tomó el humor vítreo, y los niveles de FCEV y KDR fueron detectados mediante ensayo por inmunoabsorción ligado a enzimas (ELISA). Los globos oculares fueron fijados con para formaldehido e incrustados por petrolin para tinción (H & E) hematoxilina-eosina. RESULTADOS: Cuarenta y dos ratas sobrevivieron y 16 ratas murieron en el grupo A. Ninguna de las ratas en el grupo B murió. La glucosa en la sangre a la semana, las dos semanas, y las cuatro semanas entre los dos grupos tuvo diferencias estadísticas (p < 0.05). El peso a la semana y a las dos semanas entre los dos grupos no fue diferente, pero hubo diferencia estadística a las cuatro semanas entre los dos grupos (p < 0.01). Los resultados de ELISA mostraron que los niveles de FCEV y KDR fueron 0.276 ± 0.026 ng/mLy 2.936 ± 0.295 ng/mL en el grupo A, 0.231 ± 0.021 ng/mL y 2.394 ± 0.227 ng/mL en el grupo B, respectivamente. Los niveles de FCEV y KDR del grupo A fueron superiores a los del grupo B (p < 0.05). CONCLUSIONES: Los cambios de nivel FCEV y KDR en el humor vítreo de las ratas diabéticas estaban asociados con la retinopatía temprana inducida por diabetes.