Exogenous glycosaminoglycans coat damaged bladder surfaces in experimentally damaged mouse bladder.
BACKGROUND
Interstital cystitis is often treated with exogenous glycosaminoglycans such as heparin, chondroitin sulphate (Uracyst), hyaluronate (Cystistat) or the semi-synthetic pentosan polysulphate (Elmiron). The mechanism of action is presumed to be due to a coating of the bladder surface to replace the normally present chondroitin sulphate and heparan sulphate lost as a result of the disease. This study used fluorescent labelled chondroitin sulphate to track the distribution of glycosaminoglycans administered intravesically to mouse bladder that had been damaged on the surface.


METHODS
The surfaces of mouse bladders were damaged by 3 mechanisms -- trypsin, 10 mM HCl, and protamine sulphate. Texas Red-labeled chondroitin sulphate was instilled into the bladders of animals with damaged bladders and controls instilled only with saline. Bladders were harvested, frozen, and sectioned for examination by fluorescence.


RESULTS
The normal mouse bladder bound a very thin layer of the labelled chondroitin sulphate on the luminal surface. Trypsin- and HCl-damaged bladders bound the labelled chondroitin sulphate extensively on the surface with little penetration into the bladder muscle. Protamine produced less overt damage, and much less labelling was seen, presumably due to loss of the label as it complexed with the protamine intercalated into the bladder surface.


CONCLUSIONS
Glycosaminoglycan administered intravesically does bind to damaged bladder. Given that the changes seen following bladder damage resemble those seen naturally in interstitial cystitis, the mechanisms proposed for the action of these agents is consistent with a coating of damaged bladder.
Kyker
Kimberly D
KD
Department of Urology, Oklahoma University Health Sciences Center, 940 S.L. Young Blvd, Oklahoma City, OK 73104, USA. Kimberly-kyker@ouhsc.edu
Coffman
Jean
J
Hurst
Robert E
RE
D000818:Animals; D002809:Chondroitin Sulfates / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018856:Cystitis, Interstitial / Q000188:drug therapy* / Q000378:metabolism*; D005456:Fluorescent Dyes; D006025:Glycosaminoglycans / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology*; D014966:Xanthenes / Q000627:therapeutic use
D005456:Fluorescent Dyes; D006025:Glycosaminoglycans; D014966:Xanthenes; C034657:Texas red; D002809:Chondroitin Sulfates