title: Urinary glycosaminoglycans as biomarker for urothelial injury: is it possible to discriminate damage from recovery?
abstract: OBJECTIVE
  The glycosaminoglycan (GAG) layer is referred to as a bladder protective factor. We reproduced an experimental model of urothelial damage to assess GAG metabolism in the process of injury and recovery of the urothelium.
  
  
  METHODS
  Wistar female rats were bladder catheterized and instilled with either protamine sulfate (PS groups) or sterile saline (control groups). At different days after the procedure, 24-hour urine samples were obtained. The urinary levels of hyaluronic acid (HA) and sulfated glycosaminoglycan were determined in all groups and in nonmanipulated rats (day 0). Additionally, sulfated-GAG synthesis was assessed by the incorporation of [(35)S]-inorganic sulfate. The bladders were analyzed by histochemical staining for HA and immunofluorescence for heparin sulfate and syndecan-4.
  
  
  RESULTS
  Urinary HA and sulfated-GAG were elevated after PS injection (P <0.05). A greater concentration of [(35)S]-labeled GAG in the PS group animals on the fifth day and, especially, on the seventh day represented increased GAG synthesis at these periods (P <0.05). Bladder sections from the PS group animals on day 1 showed a greater amount of HA in the urothelium. PS instillation damaged the urothelium layer of heparin sulfate and syndecan-4 seen in the control animals. On day 5, patchy areas of a restored layer were seen, and, on day 7, this layer had completely regenerated.
  
  
  CONCLUSIONS
  Urinary GAG cannot differentiate urothelial damage from recovery. Elevated levels of urinary GAG can result from either desquamation of the surface cell GAG layer or increased GAG synthesis to regenerate the damaged urothelium.
authors.affiliation: Division of Urology, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Soler
authors.forename: Homero
authors.initials: H
authors.lastname: Bruschini
authors.forename: Joao R
authors.initials: JR
authors.lastname: Martins
authors.forename: Juliana L
authors.initials: JL
authors.lastname: Dreyfuss
authors.forename: Niels O
authors.initials: NO
authors.lastname: Camara
authors.forename: Maria T
authors.initials: MT
authors.lastname: Alves
authors.forename: Katia R
authors.initials: KR
authors.lastname: Leite
authors.forename: Jose C
authors.initials: JC
authors.lastname: Truzzi
authors.forename: Helena B
authors.initials: HB
authors.lastname: Nader
authors.forename: Miguel
authors.initials: M
authors.lastname: Srougi
authors.forename: Valdemar
authors.initials: V
authors.lastname: Ortiz
mesh_terms: D000818:Animals; D015415:Biomarkers; D005260:Female; D006025:Glycosaminoglycans / Q000652:urine*; D011479:Protamines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D001745:Urinary Bladder Diseases / Q000139:chemically induced / Q000652:urine*; D019459:Urothelium / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D011479:Protamines