Urinary glycosaminoglycans as biomarker for urothelial injury: is it possible to discriminate damage from recovery?
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.
Soler
Roberto
R
Division of Urology, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
Bruschini
Homero
H
Martins
Joao R
JR
Dreyfuss
Juliana L
JL
Camara
Niels O
NO
Alves
Maria T
MT
Leite
Katia R
KR
Truzzi
Jose C
JC
Nader
Helena B
HB
Srougi
Miguel
M
Ortiz
Valdemar
V
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*
D015415:Biomarkers; D006025:Glycosaminoglycans; D011479:Protamines