title: Increased toxic urinary cations in males with interstitial cystitis: a possible cause of bladder symptoms.
abstract: OBJECTIVE
  To identify and quantify toxic urinary cations in male patients with bladder pain syndrome/interstitial cystitis versus male controls, to compare them in symptomatic patients to those significantly improved, and to evaluate cytotoxicity of these cations to cultured urothelial cells to determine whether Tamm-Horsfall protein (THP) can neutralize the cations.
  
  
  METHODS
  Isolation of cationic fraction (CFs) was achieved by solid phase extraction on urine specimens of 51 male patients with IC and 33 male controls. C18reverse-phase high-performance liquid chromatography was used to profile and quantify cationic metabolites. Major CF peaks were identified by liquid chromatography-tandem mass spectrometry. HTB-4 urothelial cells were used to determine the cytotoxicity of CFs, individual metabolites, and of metabolite mixture with THP of patient versus THP of control subject.
  
  
  RESULTS
  CF content was significantly higher in patients compared to controls (p < 0.001). Patients had higher levels of modified nucleosides, amino acids, and their derivatives compared to controls. Cytotoxicity for control versus patient mean (SEM) percent was 1.7 (2.9) % versus 63.0 (3.7) %, respectively, (p < 0.001). Cytotoxicity of metabolites was reduced in the presence of THP of control compared to THP of patient (p < 0.001).
  
  
  CONCLUSIONS
  Patients with IC had significantly higher levels of cationic metabolites with higher cytotoxicity compared to controls. THP of these patients had reduced ability to sequester cytotoxicity of cationic metabolites. Patients who significantly improved on therapy had the same levels and toxicity of cationic metabolites as symptomatic males, suggesting that these cations may be the cause of epithelial dysfunction in IC.
authors.affiliation: Department of Urology, UC San Diego Health, 200 West Arbor Dr #8897, San Diego, CA, 92103-8897, USA.
authors.forename: Sulabha
authors.initials: S
authors.lastname: Argade
authors.affiliation: Department of Urology, UC San Diego Health, 200 West Arbor Dr #8897, San Diego, CA, 92103-8897, USA.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Berecz
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Yongxuan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Urology, UC San Diego Health, 200 West Arbor Dr #8897, San Diego, CA, 92103-8897, USA. cparsons@ucsd.edu.
authors.forename: C Lowell
authors.initials: CL
authors.lastname: Parsons
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D002412:Cations / Q000652:urine*; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D018856:Cystitis, Interstitial / Q000473:pathology / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry; D016482:Urinalysis; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000473:pathology
chemical_list: D015415:Biomarkers; D002412:Cations
keywords: Bladder pain syndrome; Cytotoxicity; Interstitial cystitis; Toxic urinary cations; Urinary metabolites