Role of urinary cations in the aetiology of bladder symptoms and interstitial cystitis

摘要: Objectives To identify and characterise urinary cationic metabolites, defined as toxic factors, in patients with interstitial cystitis (IC) control subjects. To evaluate the cytotoxicity of metabolite fraction IC vs subjects individual metabolites cultured urothelial cells. Subjects Methods Cationic fractions (CFs) were isolated from urine specimens 62 33 by solid-phase extraction. CF profiled using C18 reverse-phase high performance liquid chromatography (RP-HPLC) UV detection, quantified area-under-the-peaks known standards, normalized to creatinine. RP-HPLC (LC)-mass spectrometry (MS)/tandem MS (MS/MS) used major peaks. HTB-4 cells determine CFs without Tamm–Horsfall protein (THP). Results RP-HPLC analysis showed that quantity was twofold higher compared The mean (sem) for 3.1 (0.2) 6.3 (0.5) mAU*min/μg creatinine (P < 0.001). LC-MS identified 20 metabolites. Patients had levels modified nucleosides, amino acids tryptophan derivatives −2.3 (2.0)% 36.7 (2.7)% A total 17 tested their cytotoxicity. Cytotoxicity data all significant 0.001): 1-methyladenosine (51%), 5-methylcytidine (36%), 1-methyl guanine (31%), N4-acetylcytidine (24%), N7-methylguanosine (20%) L-Tryptophan (16%). These responsible toxicity IC. significantly lower presence THP 0.001). Conclusions Major characterised found be present amounts than subjects, effectively lowered these provide new insights into factor composition well a framework which develop therapeutic strategies sequester harmful activity, may help relieve bladder symptoms associated