title: Intravesical chondroitin sulfate inhibits recruitment of inflammatory cells in an acute acid damage "leaky bladder" model of cystitis.
abstract: OBJECTIVE
  To investigate whether a physiologic effect of "glycosaminoglycan (GAG) replenishment therapy" altered recruitment of inflammatory cells in an acute bladder damage model. Replacement of the GAG layer with intravesically administered GAGs is an effective therapy for interstitial cystitis in at least some patients. Intravesically administered chondroitin sulfate was previously shown to bind to and restore the impermeability of surface-damaged ("leaky") urothelium to small ions.
  
  
  METHODS
  Rat bladders were damaged with 10 mM HCl. Negative control bladders were treated with phosphate-buffered saline. On the following day, the animal bladders were treated with 20 mg/mL chondroitin sulfate in phosphate-buffered saline, and the negative and positive controls were treated with phosphate-buffered saline alone. At 2 and 4 days after treatment with chondroitin sulfate, the rats were killed, and sections of their bladders were analyzed using toluidine blue staining for mast cell immunohistochemical labeling using antibodies against CD45 for lymphocytes and myeloperoxidase for neutrophils.
  
  
  RESULTS
  Chondroitin sulfate treatment reduced the recruitment, in a statistically significant manner, of inflammatory cells, including neutrophils and mast cells to the suburothelial space but did not alter recruitment of CD45-positive lymphocytes.
  
  
  CONCLUSIONS
  For the first time, we have demonstrated that intravesical GAG replenishment therapy also produces a physiologic effect of decreasing recruitment of inflammatory cells in an acute model of the damaged bladder. These findings support the use of intravesically administered GAG for bladder disorders that result from a loss of impermeability, including interstitial, radiation, and chemical cystitis, and possibly others as well.
authors.affiliation: Department of Urology, Oklahoma University Health Science Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Engles
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hauser
authors.forename: Shivon N
authors.initials: SN
authors.lastname: Abdullah
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Culkin
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hurst
mesh_terms: D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy / Q000209:etiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D006851:Hydrochloric Acid / Q000633:toxicity; D017493:Leukocyte Common Antigens / Q000032:analysis; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010539:Permeability; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002809:Chondroitin Sulfates; D009195:Peroxidase; D017493:Leukocyte Common Antigens; C516771:Ptprc protein, rat; D006851:Hydrochloric Acid