Intravesical administration of blebbistatin prevents cyclophosphamide‐induced toxicity of the urinary bladder in female Wistar rats

Abstract

Aims The main goal of our study was to investigate whether blebbistatin would prevent the cyclophosphamide (CYP)‐induced changes in cystometric and inflammatory parameters indicating the development of bladder inflammation and bladder overactivity. As the nature of CYP‐induced urotoxicity is inflammatory, we assume that agents presenting an anti‐inflammatory potential, such as blebbistatin, are worth special attention. Materials and Methods The experiments were carried out in female Wistar rats. Surgical procedures, cystometric investigations, measurements of bladder edema and urothelium thickness as well as biochemical analyses were performed according to the published literature. Results As expected, an acute administration of CYP (200 mg/kg, intraperitoneally) induced changes in the cystometric parameters and the levels of the tested biomarkers (ie, interleukin 1‐β, interleukin 6, interleukin 10, tumor necrosis factor‐α, nerve growth factor, brain‐derived neurotrophic factor, heparin‐binding epidermal growth factor‐like growth factor, insulin‐like growth factor‐binding protein 3, C‐X‐C motif chemokine 10, orosomucoid‐1, Tamm‐Horsfall protein, hemopexin, and occludin), indicating the development of bladder overactivity and bladder inflammation, respectively. These changes were accompanied by bladder edema and increased urothelium thickness. Intravesical infusion of blebbistatin for 7 days (125 nmol/day) prevented all symptoms of the CYP‐induced urotoxicity. Conclusions Blebbistatin might be a promising novel agent for the treatment of bladder dysfunctions, like CYP‐induced hemorrhage cystitis or bladder overactivity, since it diminished the increased urinary bladder levels of proinflammatory markers and normalized the concentrations of the anti‐inflammatory ones. This effect was accompanied by amelioration of bladder edema and permeability, and normalization of both urothelium thickness and values of the cystometric parameters.

Acute effect of cyclophosphamide on rat’s urinary bladder and the possible protective role of sulforaphane: a histological and ultrastructural study

“…21 In addition, after an acute CYP administration at a dose of 200 mg/kg Wróbe et al observed an increased urothelium thickness and bladder edema (measured by bladder permeability). 22 In the present study, the lamina propria showed dilated congested blood capillaries surrounded by perivascular cellular infiltration. This in a line with Auge et al who detected edema in the lamina propria and focal urothelial the urinary bladder injury after administration of CYP.…”

Morin-5′-Sulfonic Acid Sodium Salt (NaMSA) Attenuates Cyclophosphamide-Induced Histological Changes in Genitourinary Tract in Rats—Short Report

“…Changes in the urinary bladders were less pronounced than described by other scientists in acute models of hemorrhagic cystitis induced by intraperitoneal injections of high-dose CPX. In this kind of CPX-induced bladder toxicity urothelial necrosis, vesical edema, increased urothelium thickness, erosion, ulceration, severe hemorrhage, inflammation, leukocyte infiltration, or even fibrosis were noticed [10,25,26].…”

Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR‐4/NF‐κB, and JAK1/STAT3 signaling in cyclophosphamide‐intoxicated rats

“…Similar findings have been demonstrated in previous studies. [ 38,39 ] Data of the current study provided direct evidence of the potential role of oxidative stress in the development of hemorrhagic cystitis in CP‐treated rats and the antioxidant and anti‐inflammatory activities of ED. In this context, MDA and NO were increased and GSH, SOD, and GST were decreased in CP‐intoxicated rats, demonstrating an oxidative stress status.…”