Simvastatin Toxicity Induces Alteration of Bladder Thickness in Interstitial Cystitis Rat Model
Keywords:Bladder Pain Syndrome; Denudation; Interstitial Cystitis; Protamin Sulfate; Statin; Toxicity; Urothelial.
Background: Interstitial cystitis (IC) is a chronic inflammatory of the bladder, while statin can increase its risk.
Recently, the exact mechanism is yet known. We hypothesizedsimvastatin can induce alteration of bladder
Methods: Twenty-four female Wistar rats were aged 6-8 weeks old were divided into two groups and were
treated with simvastatin 50 mg/kg BW or carboxymethylcellulose 0.5% by oral gavage for 30 days. Each group
was then equally subdivided into three groups: control, Interstitial Cystitis (IC) day-0, and IC day-3. Either IC
or control rat group was induced by intravesical instillation of protamine sulfate or buffered saline respectively.
All animals in the control and IC day-0 group were sacrificed and collected for the bladder tissue in less than
three hours following intravesical treatment, while animals in the IC day-3 group three days after. All collected
tissue was prepared in hematoxylin-eosin staining and measured for the bladder thickness, namely the urothelial,
suburothelial, and detrusor layer by image analyzer application.
Results: There was no significant difference between the groups receiving simvastatin and placebo in the
thickness of the urothelium, suburothelium, and detrusor layers in all rat models, both control, IC0, and IC3 rats
(all p values > 0.05). However, the thickness of the urothelium layer was consistently lower in the simvastatin
group than in the placebo group in all rat models.
Conclusion: Mechanism of simvastatin toxicity on bladder tissue through urothelial denudation thus may alter
the urothelial barrier function.
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