Abstract
Chronic ketamine abuse is associated with bladder dysfunction and cystitis. However, the effects of ketamine abuse on the urinary proteome profile and the correlations among urinary proteins, urinary ketamine (and metabolites) and clinicopathological features of ketamine-induced bladder dysfunction remain to be established. Here, we recruited 56 ketamine abusers (KA) and 40 age-matched healthy controls (HC) and applied the iTRAQ-based proteomics approach to unravel quantitative changes in the urine proteome profile between the two groups. Many of the differentially regulated proteins are involved in the complement and coagulation cascades and/or fibrotic disease. Among them, a significant increase in APOA1 levels in KA relative to control samples (392.1 ± 59.9 ng/ml vs. 13.7 ± 32.6 ng/ml, p < 0.0001) was detected via ELISA. Moreover, urinary ketamine, norketamine and dehydronorketamine contents (measured via LC-SRM-MS) were found to be positively correlated with overactive bladder syndrome score (OABSS) and APOA1 levels with urinary RBC, WBC, OABSS and numeric pain rating scale in KA. Collectively, our results may aid in developing new molecular tool(s) for management of ketamine-induced bladder dysfunction. Moreover, information regarding the differentially regulated proteins in urine of KA provides valuable clues to establish the molecular mechanisms underlying ketamine-induced cystitis.
Highlights
Chronic ketamine abuse is associated with bladder dysfunction and cystitis
Using tetra-deuterated ketamine, norketamine and dehydronorketamine as internal standards, we developed a LC-selected reaction monitoring (SRM)-MS method to estimate the contents of ketamine and its metabolites in ketamine abusers (KA) urine samples (“Material and methods” section)
The detrimental effect of ketamine abuse on the lower urinary tract has been well established for more than a decade, very little is known about the urinary proteome profile and its association with ketamine-induced lower urinary tract symptoms (LUTS) in KA
Summary
Chronic ketamine abuse is associated with bladder dysfunction and cystitis. the effects of ketamine abuse on the urinary proteome profile and the correlations among urinary proteins, urinary ketamine (and metabolites) and clinicopathological features of ketamine-induced bladder dysfunction remain to be established. Information regarding the differentially regulated proteins in urine of KA provides valuable clues to establish the molecular mechanisms underlying ketamine-induced cystitis. Street ketamine abuse is a drug problem and correlated with severe urological conditions that cause a significant burden to the healthcare system[8,9]. This highlights the critical need to clarify the mechanisms underlying development of ketamine-induced lower urinary tract dysfunction, which could provide useful clues for its clinical management. It has been reported that overactive bladder syndrome caused by serious bladder inflammation is frequently observed in KA14 These observations support the correlation between OABSS and urinary ketamine and its metabolites
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