title: Resveratrol retards progression of diabetic nephropathy through modulations of oxidative stress, proinflammatory cytokines, and AMP-activated protein kinase.
abstract: BACKGROUND
  Diabetic nephropathy (DN) has been recognized as the leading cause of end-stage renal disease. Resveratrol (RSV), a polyphenolic compound, has been indicated to possess an insulin-like property in diabetes. In the present study, we aimed to investigate the renoprotective effects of RSV and delineate its underlying mechanism in early-stage DN.
  
  
  METHODS
  The protective effects of RSV on DN were evaluated in streptozotocin (STZ)-induced diabetic rats.
  
  
  RESULTS
  The plasma glucose, creatinine, and blood urea nitrogen were significantly elevated in STZ-induced diabetic rats. RSV treatment markedly ameliorated hyperglycemia and renal dysfunction in STZ-induced diabetic rats. The diabetes-induced superoxide anion and protein carbonyl levels were also significantly attenuated in RSV-treated diabetic kidney. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic renal tissues. In contrast, RSV treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group. Additionally, hyperglycemia markedly enhanced renal production of proinflammatory cytokine IL-1β. RSV reduced IL-1β but increased TNF-α and IL-6 levels in the diabetic kidneys.
  
  
  CONCLUSIONS
  Our findings suggest that RSV protects against oxidative stress, exhibits concurrent proinflammation and anti-inflammation, and up-regulates AMPK expression and activation, which may contribute to its beneficial effects on the early stage of DN.
authors.affiliation: Department and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chih-Chun
authors.initials: CC
authors.lastname: Chang
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Chang
authors.forename: Yang-Tzu
authors.initials: YT
authors.lastname: Wu
authors.forename: Jiung-Pang
authors.initials: JP
authors.lastname: Huang
authors.forename: Tzung-Hai
authors.initials: TH
authors.lastname: Yen
authors.forename: Li-Man
authors.initials: LM
authors.lastname: Hung
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D018450:Disease Progression; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D013267:Stilbenes; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol