title: Preventive effects of rutin on the development of experimental diabetic nephropathy in rats.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Key Laboratory of New Drug and Clinical Application, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Hui-hui
authors.initials: HH
authors.lastname: Hao
authors.forename: Zhu-min
authors.initials: ZM
authors.lastname: Shao
authors.forename: Dao-quan
authors.initials: DQ
authors.lastname: Tang
authors.forename: Qian
authors.initials: Q
authors.lastname: Lu
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.forename: Xiao-xing
authors.initials: XX
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005109:Extracellular Matrix / Q000378:metabolism; D050533:Glomerular Basement Membrane / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D012431:Rutin