Simvastatin protects bladder and renal functions following spinal cord injury in rats

Abstract

BackgroundUrinary bladder and renal dysfunction are secondary events associated with spinal cord injury (SCI) in humans. These secondary events not only compromise quality of life but also delay overall recovery from SCI pathophysiology. Furthermore, in experimental models the effects of SCI therapy on bladder and renal functions are generally not evaluated. In this study, we tested whether simvastatin improves bladder and renal functions in a rat model of experimental SCI.MethodsSCI was induced by controlled contusion of T9-T10 in adult female rats. Simvastatin (5 mg/Kg body weight) was administered at two hours after SCI and repeated every 24 hours until the end point. Simvastatin-treated SCI animals (simvastatin group) were compared with vehicle-treated SCI animals (vehicle group) in terms of the Basso Beattie Bresnahan score, tissue morphology, cell death, and bladder/renal functions.ResultsThe urinary bladder of vehicle animals showed a 4.3-fold increase in size and a 9-fold increase in wet weight compared to sham animals. Following SCI, the urine to plasma osmolality ratio increased initially but decreased 1 week after SCI. Hematoxylin and eosin staining of bladder tissue showed transitional epithelial hyperplasia, degeneration of lamina propria, and enlargement of tunica adventia in addition to detrusor muscle hypertrophy. Rats treated with simvastatin for 14 days displayed remarkable recovery by showing decreased bladder size and maintenance of a normal urine/plasma osmolality ratio, in addition to improved locomotion. The muscularis layer of the bladder also regained its compact nature in simvastatin animals. Moreover, SCI-induced renal caspase-3 activity was significantly decreased in the simvastatin group indicating the ability of simvastatin to reduce the renal tubular apoptosis.ConclusionPost-injury administration of simvastatin ameliorates bladder and renal dysfunction associated with SCI in rats.

Renal function in a rat model of neurogenic bladder, effect of statins and phosphodiesterase-5 inhibitors

“…Interestingly, simvastatin increased the volume at day 28 to levels very close to the sham group. The same result is reported by Shunmugavel et al [10]. Serum creatinine also decreased very close to the sham group, however, serum BUN and 24 h urine protein level decreased but stayed in significant difference with the sham group.…”

“…However, all groups had significant improvement at the end of the 1st week. The same results are reported in previous studies for statins and PDE-5 inhibitors [10,19]. However, there is no direct relation defined between motor and renal function improvement.…”

“…Therefore, the dosage of sildenafil administration in this study with regards to similar studies [19] has the same results if given in seven consecutive days, even though it has shorter period of action. The dosage of simvastatin in this study was previously shown to have effects in animal models and higher doses had toxic effects [10].…”

“…They also decrease renal inflammatory diseases through molecular pathways and declining oxidative stress [8] and the urinary stone formation [9]. They are introduced to improve the renal function particularly in spinal injuries to prevent urinary complication [10].…”

Riboflavin Treatment Reduces Apoptosis and Oxidative DNA Damage in a Rat Spinal Cord Injury Model

“…Moreover, an increase in renal caspase-3 activity caused by SCI demonstrated an increase in apoptosis of injured tissue while tadalafil blocked these effects (37). Additionally, Shunmugavel et al (38) demonstrated that SCI caused renal tubular epithelial cell loss through apoptotic mechanisms. In the aforementioned study, the renal histomorphology showed an increase in caspase-3 positive cells while simvastatin treatment prevented the increase.…”