RESUMO
Diabetic nephropathy (DN) is the main cause of morbidity and mortality in diabetes and is characterized by mesangial matrix deposition and podocytopathy, including podocyte loss. The risk factors and mechanisms involved in the pathogenesis of DN are still not completely defined. In the present study, we aimed to understand the cellular mechanisms through which activation of B2 kinin receptors contribute to the initiation and progression of DN. Stimulation of cultured rat podocytes with bradykinin (BK) resulted in a significant increase in ROS generation, and this was associated with a significant increase in NADPH oxidase (NOX)1 and NOX4 protein and mRNA levels. BK stimulation also resulted in a signicant increase in the phosphorylation of ERK1/2 and Akt, and this effect was inhibited in the presence of NOX1 and Nox4 small interfering (si)RNA. Furthermore, podocytes stimulated with BK resulted in a significant increase in protein and mRNA levels of connective tissue growth factor (CTGF) and, at the same time, a significant decrease in protein and mRNA levels of nephrin. siRNA targeted against NOX1 and NOX4 significantly inhibited the BK-induced increase in CTGF. Nephrin expression was increased in response to BK in the presence of NOX1 and NOX4 siRNA, thus implicating a role for NOXs in modulating the BK response in podocytes. Moreover, nephrin expression in response to BK was also significantly increased in the presence of siRNA targeted against CTGF. These findings provide novel aspects of BK signal transduction pathways in pathogenesis of DN and identify novel targets for interventional strategies.
Assuntos
Bradicinina/farmacologia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Proteínas de Membrana/metabolismo , Podócitos/efeitos dos fármacos , Animais , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/genética , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas de Membrana/genética , NADH NADPH Oxirredutases/genética , NADH NADPH Oxirredutases/metabolismo , NADPH Oxidase 1 , NADPH Oxidase 4 , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Podócitos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , Ratos , Receptor B2 da Bradicinina/agonistas , Receptor B2 da Bradicinina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Transfecção , Regulação para CimaRESUMO
The aim of the study was to explore the possibility that propolis can control diabetes mellitus and prevent diabetic osteopathy in rats. The study compared 60 streptozotocin (STZ)-induced diabetic rats, with ten nondiabetic rats used as a negative control. The experimental design comprised seven groups (n = 10 rats per group): (1) nondiabetic, used as a negative control; (2) nontreated, used as a positive control; (3) treated with insulin alone; (4) treated with a single dose of propolis alone; (5) treated with a double dose of propolis; (6) treated with insulin and a single dose of propolis; and (7) treated with insulin and a double dose of propolis. After 6 weeks of treatment, the rats were sacrificed. Ratios of femur ash to femur weight and of femur weight to body weight (FW/BW) were calculated and calcium (Ca), phosphorus (P), and magnesium (Mg) concentrations in femur ash were estimated and analyzed. Fasting blood glucose (FBG), plasma insulin and glucagon, serum thiobarbituric acid reactive substances (TBARS), plasma parathyroid hormone (PTH), and calcitonin levels were also estimated and analyzed. There was significant reduction in FBG in all diabetic treated rats. Similarly, higher plasma insulin levels were observed in diabetic rats treated with propolis and insulin than in nontreated diabetic rats, although plasma insulin was not comparatively higher in diabetic rats treated with insulin alone. Serum TBARS was significantly lower in the propolis treated rats than the diabetic nontreated rats. No differences in PTH and calcitonin levels were observed among treatment groups. The FW/BW ratio was significantly higher in diabetic treated groups than in control groups. Furthermore, diabetic rats treated with propolis and insulin had significantly higher Ca, P, and Mg concentrations in femoral ash than nontreated diabetic rats and diabetic rats treated with insulin alone. In conclusion, propolis has a remarkable effect on glucose homeostasis and bone mineralization.
RESUMO
The intrinsic cardiac responses to 2-months Nigella sativa (black seed) oral supplementation (800 mg/kg) in rats were investigated. The isolated hearts were perfused in a Langendorff preparation to demonstrate the effects of N. sativa on the baseline inotropic and chronotropic functions and the myocardial flow rate. N. sativa supplementation induced moderate global (homogenous) cardiac hypertrophy, evident by significant increases in left ventricular and whole heart weights as well as the relative heart weight/body weight ratio. The isolated perfused hearts of Nigella-treated rats showed enhanced levels of baseline peak tension, maximum rate of tension development, heart rate and myocardial flow rate. Moreover, there was a significant increase in the tension developed per gram left ventricular weight. The present study provides the first evidence of a physiological cardiac hypertrophy in rats induced by long term N. sativa supplementation.