Specialized pro-resolution mediators in the bladder: effects of resolvin E1 on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model.
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2024-06
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Background
One of the most common, but least studied, diabetic complication is diabetic bladder dysfunction. Current therapies include glucose control and symptom-based interventions. However, efficacy of these therapies is mixed and often have undesirable side effects. Diabetes is now known to be a chronic inflammatory disease. Specialized pro-resolving mediators are a class of compounds that promote the resolution of inflammation and have been shown to be effective in treating chronic inflammatory conditions. In this study we examine the ability of resolvin E1 to improve signs of diabetic bladder dysfunction.Methods
Male Akita mice (Type 1 diabetic) develop hyperglycemia at 4 weeks and signs of bladder underactivity by 15 weeks. Starting at 15 weeks, mice were given one or two weeks of daily resolvin E1 and compared to age-matched wild type and untreated Akita mice.Results
Resolvin E1 did not affect diabetic blood glucose after one week, although there was a slight decrease after two weeks. Diabetes decreased body weight and increased bladder weights and this was not affected by resolvin E1. Evan's blue dye extravasation (an indirect index of inflammation) was dramatically suppressed after one week of resolvin E1 treatment, but, surprisingly, had returned to diabetic levels after two weeks of treatment. Using cystometry, untreated Akita mice showed signs of underactivity (increased void volumes and intercontraction intervals). One week of resolvin E1treatment restored these cystometric findings back to control levels. After two weeks of treatment, cystometric changes were changed from controls but still significantly different from untreated levels, indicating a durable treatment effect even in the presence of increased inflammation at 2 weeks.Conclusions
Resolvin E1 has a beneficial effect on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model.Type
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Cervantes, Anissa, Francis M Hughes, Huixia Jin and J Todd Purves (2024). Specialized pro-resolution mediators in the bladder: effects of resolvin E1 on diabetic bladder dysfunction in the type 1 diabetic male Akita mouse model. BMC urology, 24(1). p. 130. 10.1186/s12894-024-01519-3 Retrieved from https://hdl.handle.net/10161/34241.
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Monty Hughes
Dr. Hughes received his Ph.D. from the Medical University of South Carolina and was a post doc at both the University of North Carolina at Chapel Hill and NIH. He then joined the faculty of the University of North Carolina at Charlotte where he rose to the rank of Associate Professor (with tenure). Following a brief stint as the director of the biology division of a start-up pharmaceutical company, he joined forces with Dr. Purves at the Medical University of South Carolina to begin this lab focused on benign urinary disorders. Dr. Hughes has been at Duke since 2015. He is currently an Assistant Professor working within the Department of Surgery and Division of Urology. He serves as the Director of the Urinary Dysfunction Laboratory which studies the role of inflammation in disorders such as bladder outlet obstruction and diabetic bladder dysfunction. In association with Dr. J Todd Purves, this lab has been instrumental in demonstrating the central importance of the NLRP3 inflammasome in sensing the biochemical stressors associated with these disorders and translating them into an inflammatory signal. This signal is ultimately responsible for changes in voiding function, denervation and fibrosis.
J Todd Purves
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