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- Title
A uro-protective agent with restorative actions on urethral and striated muscle morphology.
- Authors
Birder, Lori A.; Wolf-Johnston, Amanda; Wein, Alan J.; Grove-Sullivan, Mara; Stoltz, Donna; Watkins, Simon; Newman, Diane; Dmochowski, Roger R.; Jackson, Edwin K.
- Abstract
Purpose: Aging increases oxidative stress, which can have delirious effects on smooth and striated muscle resulting in bladder dysfunction. Consequently, in women aged over 60 years, urinary incontinence (UI) is a prevalent health problem. Despite the prevalence and consequences, UI continues to be undertreated simply because there are few therapeutic options. Methods: Here we investigated whether 8-aminoguanine (8-AG), a purine nucleoside phosphorylase (PNPase inhibitor), would restore urethra and external sphincter (EUS) muscle morphology in the aged rat. Aged (> 25 months) female Fischer 344 rats were randomized to oral treatment with 8-AG (6 weeks) or placebo, and the urethra and EUS were evaluated by electron microscopy and protein expression (western immunoblotting). Results: Aging was associated with mitochondrial degeneration in smooth and striated muscle cells as compared to young rats. We also observed a significant increase in biomarkers such as PARP, a downstream activator of oxidative/nitrosative stress. Treatment of aged rats with 8-AG normalized all abnormalities to that of a younger state. Conclusions: 8-AG, a potent inhibitor of PNPase, reverses age-related lower urinary tract morphological and biochemical changes. Our observations support the concept that 8-AG will reverse age-induced lower urinary tract disorders such as UI. These initial findings could have therapeutic implications for the prevention and treatment of age-related UI.
- Subjects
STRIATED muscle; MORPHOLOGY; WESTERN immunoblotting; URINARY organs; URINARY incontinence
- Publication
World Journal of Urology, 2021, Vol 39, Issue 7, p2685
- ISSN
0724-4983
- Publication type
Article
- DOI
10.1007/s00345-020-03492-6