Rho kinase inhibition ameliorates cyclophosphamide-induced cystitis in rats.

Content Provider	Europe PMC
Author	Wróbel, Andrzej Doboszewska, Urszula Rechberger, Ewa Rojek, Karol Serefko, Anna Poleszak, Ewa Skalicka-Woźniak, Krystyna Dudka, Jarosław Wlaź, Piotr
Abstract	Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CYP). Studies have indicated that Rho kinase (ROCK) inhibitors may suppress detrusor overactivity symptoms and possess anti-inflammatory properties. The aim of the present study was to investigate whether inhibition of ROCK reduces cystometric and histopathological changes associated with CYP-induced cystitis. The rats received GSK 269962, a ROCK inhibitor, at a dose of 30 mg/kg daily, or vehicle for 7 days. Then, acute chemical cystitis leading to bladder overactivity was induced by CYP injection (200 mg/kg i.p.). Following CYP injection, cystometric studies with physiological saline were performed. Moreover, bladder edema (by the Evans Blue dye leakage technique) and urothelium thickness were measured. CYP injection resulted in a significant increase in cystometric parameters: basal pressure, threshold pressure, bladder contraction duration, relaxation time, detrusor overactivity index, non-voiding contractions amplitude, and non-voiding contractions frequency as well as increased Evans Blue extravasation into bladder tissue, whereas micturition voiding pressure, voided volume, post-void residual, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit non-voiding contractions as well as urothelium thickness were significantly decreased in CYP-injected rats. Administration of GSK 269962 normalized the abovementioned CYP injection-induced changes. Inhibition of ROCK was found to ameliorate CYP-induced detrusor overactivity and bladder inflammation. Our data indicate uroprotective effects following ROCK inhibition, which further suggests that this strategy may become an interesting pharmacological tool to prevent urinary adverse effects in patients treated with chemotherapy using CYP.
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ISSN	00281298
Journal	Naunyn-Schmiedeberg's Archives of Pharmacology [Naunyn Schmiedebergs Arch Pharmacol]
Volume Number	390
DOI	10.1007/s00210-017-1361-8
PubMed Central reference number	PMC5411406
Issue Number	6
PubMed reference number	28220212
e-ISSN	14321912
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2017-02-21
Publisher Place	Berlin/Heidelberg
Access Restriction	Open
Rights License	Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. © The Author(s) 2017
Subject Keyword	Cyclophosphamide-induced cystitis Overactive bladder Bladder inflammation Cystometry Rho kinase inhibitor
Content Type	Text
Resource Type	Article
Subject	Medicine Pharmacology