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S‐Nitrosoglutathione protects the spinal bladder: Novel therapeutic approach to post‐spinal cord injury bladder remodeling
Author(s) -
Shunmugavel Anandakumar,
Khan Mushfiquddin,
Hughes Francis M.,
Purves J. Todd,
Singh Avtar,
Singh Inderjit
Publication year - 2015
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.22619
Subject(s) - medicine , spinal cord injury , inflammation , urination , urology , s nitrosoglutathione , spinal cord , urinary bladder , urinary system , pathology , glutathione , biochemistry , chemistry , psychiatry , enzyme
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. Neurourol. Urodynam. 34:519–526, 2015 . © 2014 Wiley Periodicals, Inc.