Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
Sci Rep. 2024 Sep 19;14(1):21898. doi: 10.1038/s41598-024-73280-4.
Chronic visceral pain disorders, such as interstitial cystitis/bladder pain syndrome (IC/BPS), are difficult to treat, and therapies are limited in number and efficacy. Emerging evidence suggests that alterations in the enzyme purine nucleoside phosphorylase (PNPase) may participate in oxidative injury and cellular damage. PNPase is important for the metabolism of 'tissue-protective' purine metabolites to 'tissue-damaging' purines that generate free radicals. The aim of this study is to test whether patients living with IC/BPS without or with Hunner lesions and irrespective of any therapies exhibit purine dysregulation with higher levels of tissue-damaging purine metabolites as measured by liquid chromatography-tandem mass spectrometry. Our results demonstrate that levels of urotoxic purine metabolites (hypoxanthine and xanthine) in IC/BPS patients with and without Hunner lesions are elevated compared to healthy controls. These findings suggest there may be pathophysiologic commonalities between patient subtypes. Furthermore, the accumulation of uroprotective purines and depletion of urodamaging purines by PNPase inhibition may be therapeutically effective in both groups of patients.
慢性内脏疼痛障碍，如间质性膀胱炎/膀胱疼痛综合征（IC/BPS），难以治疗，治疗方法数量有限且效果有限。新出现的证据表明，酶嘌呤核苷磷酸化酶（PNPase）的改变可能参与氧化损伤和细胞损伤。PNPase 对于将“组织保护”嘌呤代谢物代谢为产生自由基的“组织损伤”嘌呤很重要。本研究旨在测试是否患有 IC/BPS 的患者无论是否存在 Hunner 病变以及是否接受任何治疗，其嘌呤代谢是否失调，通过液相色谱-串联质谱法测量，表现为组织损伤性嘌呤代谢物水平升高。我们的结果表明，与健康对照组相比，有和没有 Hunner 病变的 IC/BPS 患者的尿毒性嘌呤代谢物（次黄嘌呤和黄嘌呤）水平升高。这些发现表明，患者亚群之间可能存在病理生理学共性。此外，通过 PNPase 抑制抑制尿保护嘌呤的积累和减少尿损伤嘌呤可能对两组患者都具有治疗效果。
