Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I-control, II-rats with rapamycin (RA)-induced OAB, III-rats administered IMP at a dose of 10 mg/kg/day, and IV-rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB.
International journal of molecular sciences. 2023 Oct 31*** epublish ***
Paulina Iwaniak, Piotr Dobrowolski, Jan Wróbel, Tomasz Kluz, Artur Wdowiak, Iwona Bojar, Klaudia Stangel-Wójcikiewicz, Ewa Poleszak, Artur Jakimiuk, Marcin Misiek, Łukasz Zapała, Andrzej Wróbel
Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland., Department of Functional Anatomy and Cytobiology, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka 19, 20-033 Lublin, Poland., Medical Faculty, Medical University of Lublin, 20-093 Lublin, Poland., Department of Gynecology, Gynecology Oncology and Obstetrics, Institute of Medical Sciences, Medical College of Rzeszow University, Rejtana 16c, 35-959 Rzeszow, Poland., Department of Obstetrics and Gynecology, Faculty of Health Sciences, Medical University of Lublin, Staszica 4-6, 20-081 Lublin, Poland., Department of Women's Health, Institute of Rural Health in Lublin, ul. Jaczewskiego 2, 20-090 Lublin, Poland., Department of Gynecology and Oncology, Jagiellonian University Medical College, M. Kopernika 23, 31-501 Kraków, Poland., Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland., Department of Obstetrics and Gynecology, National Medical Institute of the Ministry of Interior and Administration, Wołoska 137, 02-507 Warsaw, Poland., Clinic of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4, 02-005 Warsaw, Poland., Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland.