AIMS: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
AIMS: 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 diabeticrats were investigated. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.
Authors: Hamza Mechchate; Imane Es-Safi; Amal Amaghnouje; Smahane Boukhira; Amal A Alotaibi; Mohammed Al-Zharani; Fahd A Nasr; Omar M Noman; Raffaele Conte; El Hamsas El Youbi Amal; Hicham Bekkari; Dalila Bousta Journal: Molecules Date: 2021-01-18 Impact factor: 4.411
Authors: Yingli Jin; Yan Shi; Yinggang Zou; Chunsheng Miao; Bo Sun; Cai Li Journal: Evid Based Complement Alternat Med Date: 2014-05-08 Impact factor: 2.629
Authors: Sher Zaman Safi; Rajes Qvist; Selva Kumar; Kalaivani Batumalaie; Ikram Shah Bin Ismail Journal: Biomed Res Int Date: 2014-07-06 Impact factor: 3.411