Journal List > Korean J Urol > v.47(1) > 1069888

Kim, Shim, and Lee: The Effect of Botulinum Toxin and Resiniferatoxin on the Detrusor Overactivity Induced by Cyclophosphamide in Rat Bladder

Abstract

Purpose

The purpose of this study was to compare the effects of resiniferatoxin (RTX) and botulinum toxin (BTX) on the bladder detrusor function in a cyclophosphamide (CYP)-induced cystitis rat model.

Materials and Methods

Sprague-Dawley rats were divided into 5 groups (1: saline treated, 2: CYP and BTX treated, 3: CYP and RTX treated, 4 and 5: CYP treated and sham operated as the counterpart of groups 2 and 3, respectively, with normal saline). 100mg/kg CYP was injected every third day for five weeks. Cystometrograms were performed after the BTX and RTX treatments.

Results

1. The normal control group and the CYP-treated only group. In the CYP-treated group, the time of micturition frequency, the maximal detrusor pressure on the cystometergram (Pvesmax at CMG), the maximal detrusor pressure on the pressure-flow study (Pvesmax at pr/flow) and the episodes of irregular contractions were increased. 2. The CYP-only group and the CYP/BTX or CYP/RTXtreated groups. In the CYP/BTX or CYP/RTX treated groups, the time of micturition frequency, the Pvesmax at CMG, the Pvesmax at pr/flow and the episode of irregular contractions were decreased. 3. The CYP/BTXtreated group and the CYP/RTXtreated group. There was no statistically significant difference between the two groups regarding micturition frequency, the PvesMax at CMG and the PvesMax at pr/flow, the Dhfo and the episodes of involuntary contractions (p>0.05).

Conclusions

Intravesical administration of BTX or RTX blocked the CYP-induced detrusor overactivity as was shown by the restoration of the micturition frequency, the intravesical pressure and the involuntary contraction episodes to a control level. There was no statistically significant difference between the two groups regarding the urodynamic parameters.

Figures and Tables

Fig. 1
Triple lumen catheter, which is seated securely in the bladder neck for functional separation of the bladder and urethral activity.
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Fig. 2
Representative cystometric tracings of (A) the normal control group, (B) the cyclophosphamide (CYP)-injected group, (C) the CYP/botulinum toxin (BTX) treated group and (D) the CYP/resiniferatoxin (RTX) treated group. (A) The normal control group shows regular bladder contraction without any irregular bladder contraction. (B) The CYP-induced cystitis model shows concurrent irregular contractions (arrows) between the normal bladder contractions. (C) and (D) BTX and RTX injection, respectively, in the CYP-induced rat bladder shows recovery of regular bladder contractions without any involuntary bladder contractions.
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Fig. 3
Histological finding (H&E staining) of the normal and cyclophosphamide induces cystitis bladders after 2 weeks. (A) Histologic findings of the normal bladder, i.e., the epithelial cell lining (×100). (B) Histologic findings of the normal bladder, i.e., loose connective tissue (×200). (C) Interstitial edema and hemorrhage in the cyclophosphamide-induced cystitis bladder (×100). (D) Magnified findings of focal hemorrhage (×200). (E) Inflammatory cell infiltration in the cyclophosphamide-induced cystitis bladder (×200). (F) Wall thickening and lymphocyte infiltration in the cyclophosphamide induced cystitis bladder (×100).
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Table 1
Comparative urodynamic parameters between the normal control group and the cyclophosphamide treated group
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PvesMax at CMG (mmHg): maximal vesical pressure before the micturition, PvesMax at Pr/flow (mmHg): maximal vesical pressure during micturition, Dhfo: duration of high frequency oscillation, CYP: cyclophosphamide

Table 2
Comparative urodynamic parameters between the CYP-only group and the CYP/BTX-treated group
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PvesMax at CMG (mmHg): maximal vesical pressure before the micturition, PvesMax at Pr/flow (mmHg): maximal vesical pressure during micturition, Dhfo: duration of high frequency oscillation, CYP: cyclophosphamide, BTX: botulinum toxin

Table 3
Comparative urodynamic parameters between the CYP-only group and the CYP/RTX treated group
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PvesMax at CMG (mmHg): maximal vesical pressure before the micturition, PvesMax at Pr/flow (mmHg): maximal vesical pressure during micturition, Dhfo: duration of high frequency oscillation, CYP: cyclophosphamide, RTX: resiniferatoxin

Table 4
Comparison of the urodynamic parameters between the resiniferatoxin and botulinum toxin groups
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PvesMax at CMG (mmHg): maximal vesical pressure before the micturition, PvesMax at Pr/flow (mmHg): maximal vesical pressure during micturition, Dhfo: duration of high frequency oscillation, CYP: cyclophosphamide, BTX: botulinum toxin, RTX: resiniferatoxin

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