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

Abstract

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 mgÁkg À1 Áday À1). 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-a, and TGF-b 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-a, and TGF-b, 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.

Sirtuin 1: A Target for Kidney Diseases

“…A large body of evidence has linked TGF-β/ Smad signaling to the development and progression of renal fibrosis (34)(35)(36). Reversal of Smad3 acetylation via SIRT1 inhibited the TGF-β1-induced profibrotic response in vitro and unilateral-uretericobstruction-induced interstitial fibrosis in vivo (37)(38)(39). Furthermore, coimmunoprecipitation assay provided direct evidence of an interaction between Smad3 and SIRT1 (38,39).…”

Emerging Liver–Kidney Interactions in Nonalcoholic Fatty Liver Disease

“…Several natural (resveratrol, /-lipoic acid) and synthetic (BML-278, which is 1000-fold more potent SIRT-1 activator than resveratrol, and SRT1720 [47]) SIRT-1 activators are being evaluated: they improved experimental NAFLD [48,49] and CKD [50,51], and ameliorated steatosis and inflammatory markers in NAFLD patients [52].…”

Key roles for the small leucine-rich proteoglycans in renal and pulmonary pathophysiology

“…Chronic renal disease frequently leads to renal fibrosis [66–68]. This process involves excessive accumulation of ECM components, leading to glomerulosclerosis, tubulointerstitial fibrosis, and finally to irreversible loss of renal function and end-stage renal disease.…”