Resveratrol as a therapeutic agent for renal fibrosis induced by unilateral ureteral obstruction

Ren Fail. 2014 Mar;36(2):285-91. doi: 10.3109/0886022X.2013.844644. Epub 2013 Oct 24.


Aims: Renal fibrosis is a common outcome of chronic kidney disease. This study was designed to examine the protective effects of resveratrol (RSV) against renal fibrosis induced by unilateral ureteral obstruction (UUO). We also attempted to elucidate the potential mechanism involved.

Methods: Mice were randomly divided into three groups: sham-operated, UUO, and UUO/RSV (20 mg·kg(-1)·day(-1)). Histological changes were examined using periodic acid-Schiff and Masson's trichrome staining after 14 days. Superoxide dismutase (SOD), malondialdehyde (MDA), and 8-OHdG levels were determined using a commercially available kit. ICAM-1, TNF-α, and TGF-β levels were measured using real-time PCR. Fibronectin levels were measured by western blot, and the Smad3 acetylation and Sirt1 were examined by immunoprecipitation and western blot.

Results: Our study showed that RSV treatment significantly attenuated renal injury including extracellular matrix deposition and tubulointerstitium damage. Renal cortical mRNA levels of ICAM-1, TNF-α, and TGF-β, protein expression of fibronectin and Smad3 acetylation were significantly upregulated in the UUO group. However, treatment with RSV significantly decreased the expression of these proteins. Furthermore, RSV also decreased the levels of reactive oxygen species (ROS) including MDA and 8-OHdG, and increased the level of SOD, which protects cells against ROS damage.

Conclusion: Our findings suggest that RSV treatment inhibits oxidative stress, Smad3 acetylation, and renal interstitial fibrosis. Therefore, RSV may have potential as a therapeutic target for the treatment of chronic kidney disease.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Acetylation
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Fibronectins / metabolism
  • Fibrosis / drug therapy*
  • Fibrosis / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Glomerulus / pathology
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Reactive Oxygen Species / metabolism
  • Resveratrol
  • Smad3 Protein / metabolism
  • Stilbenes / therapeutic use*
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Ureteral Obstruction / complications*
  • Ureteral Obstruction / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Fibronectins
  • Reactive Oxygen Species
  • Smad3 Protein
  • Stilbenes
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Malondialdehyde
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Resveratrol