title: Atorvastatin ameliorates renal tissue damage in unilateral ureteral obstruction.
abstract: OBJECTIVE
  The current study was done to determine whether atorvastatin, the HMGCoA (3-hydroxy-3-methylglutaryl CoA) reductase inhibitor, could decrease renal transforming growth factor-beta (TGF-beta) levels in unilateral ureteral obstruction (UUO) and concomitantly affect renal tissue damage in UUO.
  
  
  METHODS
  Atorvastatin (20 mg/kg) was administered to rats 1 day prior to UUO and every day thereafter. Kidneys were harvested at day 14 after UUO. Tissue TGF-beta was measured by bioassay using mink lung epithelial cells. Renal tubular proliferation and apoptosis were detected by immunostaining proliferating cell nuclear antigen and polyclonal antisingle strand DNA antibody, respectively. Fibrosis was assessed by measuring collagen deposition with trichrome stained slides. Interstitial leukocyte was detected by immunostaining CD45.
  
  
  RESULTS
  TGF-beta bioassay showed that the obstructed kidney in the control group contained significantly higher TGF-beta than the unobstructed kidney in the control group (mean +/- SD 79.1 +/- 48.5 vs 28.7 +/- 13.7 pg/mg tissue) and atorvastatin significantly decrease tissue TGF-beta in the obstructed kidney (53.4 +/- 37.0 pg/mg tissue). Immunostaining polyclonal antisingle strand DNA antibody demonstrated that the obstructed kidney in the control group has significantly more tubular apoptosis than the unobstructed counterpart (4.8 +/- 2.8 vs 2.1 +/- 1.2 nuclei per high power field) and atorvastatin significantly decreased renal tubular apoptosis in the obstructed kidney (1.1 +/- 0.7 nuclei per high power field). In addition, immunostaining proliferating cell nuclear antigen showed that the obstructed kidney in the atorvastatin group had significantly more renal tubular proliferation than the obstructed kidney in the control group (48.7 +/- 20.8 vs 17.3 +/- 10.6 per high power field). Control obstructed kidney showed significantly more fibrosis, which was also blunted by atorvastatin.
  
  
  CONCLUSIONS
  Atorvastatin significantly decreases tissue TGF-beta, resulting in a decrease in tubular damage and interstitial fibrosis. This suggests that atorvastatin is a promising agent for preventing renal tubular damage in UUO.
authors.affiliation: Department of Urology, National Defense Medical College, Saitama and Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Mizuguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Miyajima
authors.forename: Takeo
authors.initials: T
authors.lastname: Kosaka
authors.forename: Takako
authors.initials: T
authors.lastname: Asano
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Asano
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hayakawa
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D014517:Ureteral Obstruction / Q000150:complications* / Q000378:metabolism* / Q000473:pathology
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D016212:Transforming Growth Factor beta; D000069059:Atorvastatin