Abstract
Chronic inflammation is a potential systemic risk factor for many bladder dysfunctions, including interstitial cystitis (IC). However, the underlying mechanism through which a healthy bladder protects itself from inflammatory triggers remains unknown. In this study, we identified odor compounds in urine obtained from IC patients and healthy controls. Using comprehensive solid-phase microextraction-gas chromatography-time-of-flight-mass spectrometry (SPME-GC-TOF-MS) profiling and bioinformatics, we found that levels of urinary volatile metabolites, such as menthol, were significantly reduced in IC patients, compared to healthy controls. In an attempt to understand the mechanistic meaning of our volatile metabolites data and the role of menthol in the immune system, we performed two independent experiments: (a) cytokine profiling, and (b) DNA microarray. Our findings suggest that lipopolysaccharide (LPS)-stimulated inflammatory events, such as the production and secretion of inflammatory cytokines (e.g., TNF-α, IL-6, and IL-1β) and the activation of NF-κB and associated proteins within a large signaling network (e.g., Akt, TLR1, TNFAIP3, and NF-κB), are suppressed by the presence of menthol. These findings broaden our knowledge on the role of urinary menthol in suppressing inflammatory events and provide potential new strategies for alleviating both the odor and inflammation associated with IC.
Highlights
Interstitial cystitis (IC) is a clinical condition that presents itself as sensory hypersensitivity of unknown cause and is characterized by frequent urination, bladder discomfort, and pelvic pain[1]
Odor consists of various volatile organic chemical compounds (VOCs), which can be identified through mass spectrometry
We discovered that urinary menthol decreased in interstitial cystitis (IC) patients and that these reduced levels are potentially linked to the chronic inflammation commonly observed in IC
Summary
Interstitial cystitis (IC) is a clinical condition that presents itself as sensory hypersensitivity of unknown cause and is characterized by frequent urination, bladder discomfort, and pelvic pain[1]. Metabolomics focuses on utilizing and analyzing metabolites and biomarkers as signals for cellular states These biological biomarkers have been used to understand the metabolic changes that occur over time in a variety of diseases[5]. Urine contains a multitude of water-soluble waste products filtered through the kidneys and eliminated from the body via micturition It contains many metabolites, such as urea (from amino acid metabolism), inorganic salts (chloride, sodium, and potassium), creatinine, ammonia, organic acids, water-soluble toxins, and urobilin. While this complexity can make urine analysis difficult, the potential information that can result will be very beneficial, and progress in the field has been promising. Given our previous findings that IC patients may have a distinct metabolism[13,14], we hypothesized that urine from IC patients might contain a distinguishing VOC signature that is reflective of disease conditions
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