Potentilla chinensis aqueous extract attenuates cyclophosphamide-induced hemorrhagic cystitis in rat model

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作者
Kajetan Juszczak
Jan Adamowicz
Łukasz Zapała
Tomasz Kluz
Przemysław Adamczyk
Artur Wdowiak
Iwona Bojar
Marcin Misiek
Magdalena Emilia Grzybowska
Klaudia Stangel-Wójcikiewicz
Ewa Poleszak
Marta Pokrywczyńska
Tomasz Drewa
Andrzej Wróbel
机构
[1] Nicolaus Copernicus University,Department of Urology and Andrology, Collegium Medicum
[2] Nicolaus Copernicus University,Department of Regenerative Medicine, Collegium Medicum
[3] Medical University of Warsaw,Clinic of General, Oncological and Functional Urology
[4] Medical College of Rzeszow University,Department of Gynecology and Obstetrics, Institute of Medical Sciences
[5] Nicolaus Copernicus Hospital,Department of General and Oncological Urology
[6] Medical University of Lublin,Chair of Obstetrics and Gynecology, Faculty of Health Sciences
[7] Institute of Rural Health in Lublin,Department of Women’s Health
[8] Holy Cross Cancer Center,Department of Gynecologic Oncology
[9] University of Gdańsk,Department of GynecologyGynecological Oncology and Gynecological Endocrinology, Medical
[10] Jagiellonian University Medical College,Department of Gynecology and Oncology
[11] Medical University of Lublin,Chair and Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing
[12] Medical University of Lublin,Second Department of Gynaecology
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摘要
Cyclophosphamide (CYP) damages all mucosal defence lines and induces hemorrhagic cystitis (HC) leading to detrusor overactivity. Patients who undergo combined chemio-radiotherapy are at higher risk of HC. Potentilla chinensis extract (PCE) prevent oxidative stress-dependent diseases. Thus, the aim of the study was to investigate the effect of PCE on urinary bladder function in CYP-induced HC in preclinical study. 60 rats were divided into 4 groups, as follows: I—control, II—rats with CYP-induced HC, III—rats received PCE in dose of 500 mg/kg, and IV—rats with CYP-induced HC which received PCE in dose of 500 mg/kg. PCE or vehicle were administered orally for 14 days. The cystometry was performed 3 days after the last dose of the PCE. Next, urothelium thickness and oedema measurement and biochemical analyses were performed. Cyclophosphamide induced hemorrhagic cystitis. PCE had no influence on the urinary bladder function and micturition cycles in normal rats. PCE diminished the severity of CYP-induced hemorrhagic cystitis. In the urothelium the cyclophosphamide induced the elevation of CGRP, TNF-α, IL-6, IL-1β, OTC3, NIT, and MAL. Also, the level of T-H protein, HB-EGF, and ZO1 was decreased. Moreover, the level of ROCK1 and VAChT in detrusor muscle increased. cyclophosphamide caused an increased concentration of BDNF and NGF in the urine. In turn, PCE in cyclophosphamide-induced hemorrhagic cystitis caused a reversal of the described biochemical changes within urothelium, detrusor muscle and urine. PCE attenuates detrusor overactivity. In conclusion, our results revealed that PCE attenuates detrusor overactivity in case of cyclophosphamide-induced hemorrhagic cystitis. The potential properties of PCE appear to be important in terms of preventing of oxidative stress-dependent dysfunction of urinary bladder. PCE may become a potential supportive treatment in patient to whom cyclophosphamide-based chemotherapy is used.
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