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

Abstract

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.

Protective effects of dantrolene and methylprednisolone against spinal cord injury-induced early oxidative damage in rabbit bladder: A comparative experimental study

“…16 Anti-inflammatory treatment may be beneficial in the treatment of neurogenic bladder by inhibiting the inflammatory response. 2,27 Studies have reported that antioxidants such as DNT after SCI contribute to healing of mesenteric lesions by reducing hemorrhage and immunocyte infiltration in the bladder. 2,16,20 In our current study, unlike the literature, there was no difference between the experimental groups in terms of inflammation in the bladder.…”

Multiple organ dysfunction and systemic inflammation after spinal cord injury: a complex relationship

“…Application of antioxidant vitamin C and activation of adrenoreceptors protected rat kidneys from SCI-induced damage by suppressing NF-κB signaling and pro-inflammatory cytokine expression [ 94 , 97 ]. Oral administration of anti-inflammatory small-molecule S-nitrosoglutathione can promote recovery of neurogenic bladder via inhibition of inflammatory responses [ 98 ]. Oxidants such as dantrolene and quercetin are able to ameliorate urinary bladder lesions after SCI by decreasing bladder hemorrhage and immune cell infiltration [ 101 , 102 ].…”

S-Nitrosoglutathione ameliorates acute renal dysfunction in a rat model of lipopolysaccharide-induced sepsis

“…Several reports from our laboratories and others have shown that GSNO has antioxidant, anti‐inflammatory and neuroprotective properties in various animal models, including experimental autoimmune disease, TBI, stroke, SCI and Alzheimer's disease . Recently, we showed that the anti‐inflammatory property of GSNO is renoprotective in rats with SCI . In this study, we hypothesized that exogenous administration of GSNO to LPS‐induced endotoxemic rats would ameliorate renopathological outcomes and that GSNO‐mediated renoprotection would occur through increased expression of anti‐inflammatory cytokine IL‐10, increased levels of antioxidant GSH and decreased expression of the pro‐inflammatory mediators TNF‐α and iNOS.…”