A uro-protective agent with restorative actions on urethral and striated muscle morphology.
World J Urol
; 39(7): 2685-2690, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-33078215
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Uretra
/
Músculo Estriado
/
Guanina
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article