Effect of Simvastatin to Bladder Detrusor Senescence Acitivity in Protamin Sulfate-Induced Intersititial Cystitis Rat Model
European Journal of Molecular & Clinical Medicine,
2020, Volume 7, Issue 10, Pages 2431-2440
AbstractStatin can increase the risk of interstitial cystitis. Recently, the exact mechanism is yet known. We hypothesize that cellular senescence, particularly in the detrusor muscle cells contributes to the mechanism. In this study, we aim to investigate the effect of simvastatin on bladder detrusor senescence activity in the protamine sulfate-induced interstitial cystitis rat model. Thirty-seven female Wistar rats aged 6-8 weeks old were included and divided into three groups. They were treated with simvastatin 10 mg/kg BW (n=12), simvastatin 50 mg/kg BW (n=13), and the solvent carboxymethylcellulose (CMC) 0.5% (n=12) by oral gavage for 30 days. Each group was then equally subdivided into three groups: control, IC day-0, and IC day-3. The IC rat group was induced by protamine sulfate, while the control group was treated with buffered saline intravesical treatment. In less than three hours after intravesical treatment, all animals in the control and IC day-0 group were sacrificed to collect their bladder tissue. Otherwise, animals in the IC day-3 group were sacrificed three days after intravesical treatment. All collected tissue was measured for senescence marke β-Galactosidase 1 (GLB1) expression by immunohistochemistry procedure. In the control group, the GLB1 expression in rat treated with simvastatin 50 mg/kg BW was 20.12 ± 5.77 % and highest than the rat treated with other treatment, although the difference not significant (p=0.812). In the IC day-0 and IC day-3 group, the GLB1 expression in rat treated with simvastatin 10 mg/kg BW and CMC 0.5% were higher than in the control group, otherwise, the GLB1 expression in rat treated with simvastatin 50 mg/kg BW was lower than in the control group, although not significant (p>0.05). We conclude that a higher dose of simvastatin can increase the bladder detrusor senescence expression along with their apoptotic activity in the presence of urinary leakage.
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