title: Eplerenone-mediated aldosterone blockade prevents renal fibrosis by reducing renal inflammation, interstitial cell proliferation and oxidative stress.
abstract: OBJECTIVE
  Prolonged elevation of serum aldosterone leads to renal fibrosis. Inflammation also plays a role in the pathogenesis of renal disease. We used a rat model of interstitial renal fibrosis to test the hypothesis that eplerenone-mediated aldosterone blockade prevents renal fibrosis due to its anti-inflammatory and anti-proliferative effects.
  
  
  METHODS
  Eplerenone (a selective aldosterone blocker) or vehicle (control), was given to male Wistar rats (50 mg/kg, twice daily) for 7 days before unilateral ureteral obstruction (UUO) and for an additional 28 days after surgery. Body weight, blood pressure, renal histo-morphology, immune-staining for macrophages, monocyte chemotactic protein-1, proliferating cell nuclear antigen, α-smooth muscle actin, and serum and urine markers of renal function and oxidative stress were determined for both groups on 7, 14, and 28 days after surgery.
  
  
  RESULTS
  Epleronone had no effect on body weight or blood pressure. However, eplerenone inhibited the development of renal fibrosis, inflammation (macrophage and monocyte infiltration), interstitial cell proliferation, and activation of interstitial cells (α-SMA expression). Epleronone also reduced oxidative stress.
  
  
  CONCLUSIONS
  The anti-fibrotic effect of eplerenone appears to be unrelated to its effect on blood pressure. Eplerenone inhibits renal inflammation, interstitial cell proliferation, phenotypic changes of interstitial cells, and reduces oxidative stress.
authors.affiliation: Department of internal medicine , Guangzhou City Red Cross Hospital, Guangdong Province Guangzhou City 510220, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.forename: Xiaoshi
authors.initials: X
authors.lastname: Zhong
authors.forename: Yuebin
authors.initials: Y
authors.lastname: Shao
authors.forename: Ashio
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D000077545:Eplerenone; D005355:Fibrosis; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D009395:Nephritis, Interstitial / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone