title: Does cyclooxygenase-2 inhibitor prevent renal tissue damage in unilateral ureteral obstruction?
abstract: OBJECTIVE
  We determined whether the cyclooxygenase-2 inhibitor etodolac affects renal tubular damage and interstitial fibrosis in unilateral ureteral obstruction.
  
  
  METHODS
  Etodolac (10 mg./kg.) was administered to rats 1 day before unilateral ureteral obstruction and every day thereafter. Kidneys were harvested at day 14 after unilateral ureteral obstruction. Tissue transforming growth factor-beta and prostaglandin E2 were measured by bioassay using mink lung epithelial cells and enzyme linked immunosorbent-sandwich assay. Renal tubular proliferation and apoptosis were detected by immunostaining with proliferating cellular nuclear antigen and by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling, respectively. Cyclooxygenase-2 expression was detected by immunohistochemistry. Fibrosis was assessed by measuring collagen deposition in trichrome stained slides.
  
  
  RESULTS
  Bioassay showed that in the control group obstructed kidneys contained significantly higher mean transforming growth factor-beta1 than unobstructed kidneys (79.1 +/- 8.3 versus 33.6 +/- 4.2 ng./gm. tissue) and etodolac significantly decrease the mean value in obstructed kidneys (46.2 +/- 10.0 ng./gm. tissue). Assay demonstrated that obstructed control kidneys had significantly more mean tubular apoptosis than their unobstructed counterparts (26.6 +/- 5.4 versus 2.2 +/- 1.4 nuclei per high power field) and etodolac significantly decreased mean renal tubular apoptosis in the obstructed kidneys (16.2 +/- 1.9 nuclei per high power field). In addition, immunostaining with proliferating cellular nuclear antigen showed that obstructed kidneys in the control group had significantly more mean renal tubular proliferation than unobstructed kidneys (9.8 +/- 3.4 versus 3.9 +/- 0.1 per high power field) and etodolac significantly increased mean proliferating renal tubule in the obstructed kidneys (24.9 +/- 4.3 per high power field). Control obstructed kidneys had significantly more fibrosis and prostaglandin E2 production, which were also significantly blunted by etodolac.
  
  
  CONCLUSIONS
  The cyclooxygenase-2 inhibitor etodolac significantly reduces tissue transforming growth factor-beta, resulting in decreased tubular damage and interstitial fibrosis. This finding suggests that etodolac is a promising agent for preventing renal tissue damage in unilateral ureteral obstruction.
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Miyajima
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: T
authors.initials: T
authors.lastname: Asano
authors.forename: K
authors.initials: K
authors.lastname: Seta
authors.forename: A
authors.initials: A
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Hayakawa
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000096:biosynthesis; D017308:Etodolac / Q000627:therapeutic use*; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control; D020287:In Situ Nick-End Labeling; D007527:Isoenzymes / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014517:Ureteral Obstruction / Q000150:complications* / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D018809:Proliferating Cell Nuclear Antigen; D016212:Transforming Growth Factor beta; D017308:Etodolac; D003094:Collagen; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone