Preventive effects of rutin on the development of experimental diabetic nephropathy in rats.

Diabetic nephropathy (DN) is an important microvascular complication and one of the main causes of end-stage renal disease. In this study, the preventive effect and mechanism of rutin on the development of DN in streptozotocin (STZ)-induced diabetic rats were investigated. After an early DN model was induced by STZ, rats were orally administered rutin at 3 doses for 10 weeks. Fasting blood glucose, creatinine (Cr), blood urea nitrogen (BUN), urine protein, kidney index, antioxidase, advanced glycosylation end products (AGEs), extracellular matrix (ECM) including collagen IV and laminin, connective tissue growth factor (CTGF), phosphorylated Smad 2/3 (p-Smad 2/3) and Smad 7 (p-Smad 7), and transforming growth factor-β(1) (TGF-β(1)) were determined by different methods, respectively. The ultrastructural morphology was observed by a transmission electron microscope. Compared with the DN group, rutin decreased the levels of fasting blood glucose, Cr, BUN, urine protein, the intensity of oxidative stress and p-Smad 7 significantly. The expression of AGEs, collagen IV and laminin, TGF-β(1), p-Smad 2/3 and CTGF was inhibited by rutin significantly. Moreover, rutin was observed to inhibit proliferation of mesangial cells and decrease thickness of glomerular basement membrane (GBM) by electron microscopy. The preventive effect of rutin on the development of DN is closely related to oxidative stress and the TGF-β(1)/Smad/ECM and TGF-β(1)/CTGF/ECM signaling pathways. Those results suggest that rutin can prevent the development of experimental DN in rats.

Hao HH ，Shao ZM ，Tang DQ ，Lu Q ，Chen X ，Yin XX ，Wu J ，Chen H ... -  《-》

Effects of Ginkgo biloba on prevention of development of experimental diabetic nephropathy in rats.

Lu Q ，Yin XX ，Wang JY ，Gao YY ，Pan YM ... -  《-》

Connective tissue growth factor antagonizes transforming growth factor-β1/Smad signalling in renal mesangial cells.

O'Donovan HC ，Hickey F ，Brazil DP ，Kavanagh DH ，Oliver N ，Martin F ，Godson C ，Crean J ... -  《-》

Quercetin ameliorates diabetic nephropathy by reducing the expressions of transforming growth factor-β1 and connective tissue growth factor in streptozotocin-induced diabetic rats.

Lai PB ，Zhang L ，Yang LY 《-》

Resveratrol ameliorates early diabetic nephropathy associated with suppression of augmented TGF-β/smad and ERK1/2 signaling in streptozotocin-induced diabetic rats.

Diabetic nephropathy (DN) is the major cause of end-stage renal disease. The early changes in DN are characterized by an increased in kidney size, glomerular volume, and kidney function, followed by the accumulation of glomerular extracellular matrix, increased urinary albumin excretion (UAE), glomerular sclerosis, and tubular fibrosis. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. In the present study, we examined the beneficial effects of RSV on DN and explored the possible mechanism of RSV action. Male Sprague-Dawley rats were injected with streptozotocin at 65mg/kg body weight. The induction of diabetes mellitus (DM) was confirmed by a fasting plasma glucose level ≥300mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75mg/kg body weight 3 times a day for 8 weeks. Animals were sacrificed and kidney histology was examined by microscopy. Urinary albumin excretion, glomerular hypertrophy and expressions of fibronectin, collagen IV, and TGF-β in the glomeruli were alleviated in RSV-treated DM rats, but not in untreated DM rats. In addition, RSV treatment reduced the thickness of the glomerular basement membrane (GBM) to the original thickness and increased nephrin expressions to normal levels in DM rats. Moreover, RSV inhibited phosphorylation of smad2, smad3 and ERK1/2 in diabetic rat kidneys. This is the first report showing that RSV alleviates early glomerulosclerosis in DN through TGF-β/smad and ERK1/2 inhibition. In addition, podocyte injuries of diabetic kidneys are lessened by RSV.

Chen KH ，Hung CC ，Hsu HH ，Jing YH ，Yang CW ，Chen JK ... -  《-》