S-Nitrosoglutathione protects the spinal bladder: novel therapeutic approach to post-spinal cord injury bladder remodeling.

Journal Article (Journal Article)

AIMS: Bladder and renal dysfunction are secondary events of the inflammatory processes induced by spinal cord injury (SCI). S-Nitrosoglutathione (GSNO), an endogenous nitrosylating agent is pleiotropic and has anti-inflammatory property. Hence, GSNO ameliorates inflammatory sequelae observed in bladder and renal tissues after SCI. Thus, we postulate that GSNO will improve the recovery of micturition dysfunction by quenching the bladder tissue inflammation associated with SCI. METHODS: Contusion-based mild SCI was induced in female Sprague-Dawley rats. Sham operated rats served as the controls. SCI rats were gavaged daily with GSNO (50 µg/kg) or vehicle. Bladder function was assessed by urodynamics at 2 and 14 days following SCI. Urine protein concentration and osmolality were measured. Bladder and kidney tissues were analyzed by histology and immunofluorescence for a variety of endpoints related to inflammation. RESULTS: Two days after SCI, urodynamics demonstrated a hyperreflexive bladder with overflow and no clear micturition events. By Day 14, vehicle animals regained a semblance of a voiding cycle but with no definite intercontraction intervals. GSNO-treated SCI-rats showed nearly normal cystometrograms. Vehicle-treated SCI rats had increased bladder wet weight, proteinuria, and urine osmolality at Day 14, which was reversed by GSNO treatment. In addition, the SCI-induced increase in immune cell infiltration, collagen deposition, iNOS, and ICAM-1 expression and apoptosis were attenuated by GSNO. CONCLUSIONS: These results indicate that oral administration of GSNO hastens the recovery of bladder function after mild contusion-induced SCI through dampening the inflammation sequelae. These findings also suggest that GSNO-mediated redox modulation may be a novel therapeutic target for the treatment of mild SCI-induced renal and bladder dysfunction.

Full Text

Duke Authors

Cited Authors

  • Shunmugavel, A; Khan, M; Hughes, FM; Purves, JT; Singh, A; Singh, I

Published Date

  • August 2015

Published In

Volume / Issue

  • 34 / 6

Start / End Page

  • 519 - 526

PubMed ID

  • 24853799

Pubmed Central ID

  • PMC4285587

Electronic International Standard Serial Number (EISSN)

  • 1520-6777

Digital Object Identifier (DOI)

  • 10.1002/nau.22619


  • eng

Conference Location

  • United States