{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:30:28Z","timestamp":1774618228627,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funds for Statutory Activity of the Medical University of Lublin, Poland."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The purpose of our study was to assess if spinacetin (SPC), a flavonoid found in spinach, can alleviate the cyclophosphamide (CYP)-induced changes in cystometric and inflammatory parameters indicative of the development of hemorrhagic cystitis. The animal experiments were conducted in female Wistar rats. The cohort of 60 animals was grouped as follows: I\u2014control, II\u2014CYP group, III\u2014SPC group, and IV\u2014CYP + SPC group. The cystometry and biochemical analyses were performed after a fortnight of SPC administration. SPC was found to restore normal cystometric parameters in CYP-induced cystitis and, similarly, it normalized c-Fos expression changes in the central micturition regions. SPC further prevented a massive increase in the bladder wall thickness\/permeability due to exposition to CYP administration. CYP instillation resulted in the elevation of biomarkers found in urine (brain-derived neurotrophic factor, BDNF, and nerve growth factor, NGF), and in the bladder detrusor muscle (Rho kinase and vesicular acetylcholine transporter, VAChT), which were successfully restored after administration of SPC. As for the biomarkers in the bladder urothelium, the CYP-induced increases in TNF-\u03b1, IL-1\u03b2, IL-6, calcitonin gene-related peptide (CGRP), malondialdehyde, 3-nitrotyrosine, insulin-like growth factor-binding protein 3 (IGFBP-3), occludin, organic cation transporter 3 (OCT-3), orosomucoid-1 (ORM1), pituitary adenylate cyclase receptor 1 (PAC1), synaptosomal-associated protein 23 (SNAP23), SNAP25, and synaptic vesicle glycoprotein (SV2A) levels were attenuated by SPC. Finally, CYP administration resulted in a decrease in the heparin-binding EGF-like growth factor (HB-EGF), hemopexin (HPX), T-H protein, and tight junction protein (Z01), and we noted the successful restoration of all these changes in concentrations after application of SPC. In summary, SPC robustly mitigated cyclophosphamide (CYP)-induced cystometric dysfunction and biochemical alterations characteristic of iatrogenic hemorrhagic cystitis. These findings position SPC as a compelling therapeutic candidate and warrant further translational investigation for the management of CYP-induced bladder injury.<\/jats:p>","DOI":"10.3390\/ijms27073056","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:45:53Z","timestamp":1774615553000},"page":"3056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plant-Derived Spinacetin Mitigates Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4168-9410","authenticated-orcid":false,"given":"Jan","family":"Wr\u00f3bel","sequence":"first","affiliation":[{"name":"Medical Faculty, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7340-280X","authenticated-orcid":false,"given":"\u0141ukasz","family":"Zapa\u0142a","sequence":"additional","affiliation":[{"name":"Clinic of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4 Lindleya 4 St., 02-005 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7132-0453","authenticated-orcid":false,"given":"Grzegorz","family":"Niemczyk","sequence":"additional","affiliation":[{"name":"Clinic of General, Oncological and Functional Urology, Medical University of Warsaw, Lindleya 4 Lindleya 4 St., 02-005 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8816-0290","authenticated-orcid":false,"given":"Anna","family":"Bogaczyk","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Gynecology Oncology and Obstetrics, Faculty of Medicine, University of Rzeszow, Tadeusza Rejtana 16 c St., 35-959 Rzeszow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-3986","authenticated-orcid":false,"given":"Tomasz","family":"Kluz","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Gynecology Oncology and Obstetrics, Faculty of Medicine, University of Rzeszow, Tadeusza Rejtana 16 c St., 35-959 Rzeszow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-2345","authenticated-orcid":false,"given":"Artur","family":"Wdowiak","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Faculty of Health Sciences, Medical University of Lublin, Staszica 4-6 St., 20-081 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Misiek","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, Jan Kochanowski University, 25-369 Kielce, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3171-225X","authenticated-orcid":false,"given":"Iwona","family":"Bojar","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s Health, Institute of Rural Health in Lublin, Jaczewskiego 2 St., 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4359-3953","authenticated-orcid":false,"given":"Ewa","family":"Poleszak","sequence":"additional","affiliation":[{"name":"Department of Applied and Social Pharmacy, Laboratory of Preclinical Testing, Medical University of Lublin, Chod\u017aki 1 St., 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Misiek","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Holy Cross Cancer Center, 25-377 Kielce, Poland"},{"name":"Faculty of Medicine, Collegium Medicum, Jan Kochanowski University in Kielce, 25-369 Kielce, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinga","family":"Gawe\u0142","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Poznan University of Medical Sciences, Rokietnicka 3 Str., 60-806 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5772-0573","authenticated-orcid":false,"given":"Andrzej","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8 St., 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nrclinonc.2009.146","article-title":"Cyclophosphamide and cancer: Golden anniversary","volume":"6","author":"Emadi","year":"2009","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1200\/JCO.2005.12.516","article-title":"Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia","volume":"23","author":"Wierda","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/1097-0142(19880201)61:3<451::AID-CNCR2820610308>3.0.CO;2-G","article-title":"Cyclophosphamide-induced hemorrhagic cystitis. A review of 100 patients","volume":"61","author":"Stillwell","year":"1988","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1177\/106002809502900914","article-title":"Efficacy of mesna for prevention of hemorrhagic cystitis after high-dose cyclophosphamide therapy","volume":"29","author":"Haselberger","year":"1995","journal-title":"Ann. Pharmacother."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wang, R., Hong, M., Huang, J., Zhou, N., Zhang, Y., Xu, S., Liu, J., Yuan, J., Zhang, L., and Huang, L. (2021). Low-Dose Cyclophosphamide Induces Nerve Injury and Functional Overactivity in the Urinary Bladder of Rats. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.715492"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/sj.bmt.1705474","article-title":"Treatment of post-hematopoietic stem cell transplantation hemorrhagic cystitis with intravesicular sodium hyaluronate","volume":"38","author":"Miodosky","year":"2006","journal-title":"Bone Marrow Transpl."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.urolonc.2021.05.017","article-title":"Cyclophosphamide-associated bladder cancers and considerations for survivorship care: A systematic review","volume":"39","author":"Chou","year":"2021","journal-title":"Urol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wrobel, A., Zapala, L., Kluz, T., Rogowski, A., Misiek, M., Juszczak, K., Sienko, J., Gold, D., Stangel-Wojcikiewicz, K., and Poleszak, E. (2021). The Potential of Asiatic Acid in the Reversion of Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115853"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wrobel, A., Zapala, L., Zapala, P., Piecha, T., and Radziszewski, P. (2020). The effect of O-1602, a GPR55 agonist, on the cyclophosphamide-induced rat hemorrhagic cystitis. Eur. J. Pharmacol., 882.","DOI":"10.1016\/j.ejphar.2020.173321"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1002\/rcm.7967","article-title":"Rapid ultra-high-performance liquid chromatography\/quadrupole time-of-flight tandem mass spectrometry and selected reaction monitoring strategy for the identification and quantification of minor spinacetin derivatives in spinach","volume":"31","author":"Singh","year":"2017","journal-title":"Rapid Commun. Mass. Spectrom."},{"key":"ref_11","first-page":"83","article-title":"Pharmacological Activity of Spinacia oleracea Linn.\u2013A Complete Overview","volume":"2","author":"Metha","year":"2014","journal-title":"Asian J. Pharm. Res. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Flores-Estrada, J., Cano-Martinez, A., Ibarra-Lara, L., Jimenez, A., Palacios-Reyes, C., Garcia, L.J.P., Ortiz-Lopez, M.G., Rodriguez-Pena, O.N., and Hernandez-Portilla, L.B. (2025). Spinach Extract Reduces Kidney Damage in Diabetic Rats by Impairing the AGEs\/RAGE Axis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26104730"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/ptr.1379","article-title":"Ternatin, a flavonoid, prevents cyclophosphamide and ifosfamide-induced hemorrhagic cystitis in rats","volume":"18","author":"Vieira","year":"2004","journal-title":"Phytother. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liu, D., and Zhao, L. (2022). Spinacetin alleviates doxorubicin-induced cardiotoxicity by initiating protective autophagy through SIRT3\/AMPK\/mTOR pathways. Phytomedicine, 101.","DOI":"10.1016\/j.phymed.2022.154098"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bibi, A., Zhang, H.X., Hayat, M.F., Alzahrani, K.J., Alsharif, K.F., and Alzahrani, F.M. (2025). Therapeutic potential of spinacetin against cadmium-exacerbated hepatic ischemia\/reperfusion injury via regulating AMPK\/SIRT1\/PGC-1alpha and NF-kappaB pathway. J. Trace Elem. Med. Biol., 92.","DOI":"10.1016\/j.jtemb.2025.127757"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Jaiswal, V., and Lee, H. (2026). Spinacetin, an Anti-Inflammatory Natural Compound with Multiple Pharmacological Properties. Curr. Issues Mol. Biol., 48.","DOI":"10.3390\/cimb48030250"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/nau.21108","article-title":"Rodent models for urodynamic investigation","volume":"30","author":"Andersson","year":"2011","journal-title":"Neurourol. Urodyn."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1002\/nau.21180","article-title":"Functional characterization of a chronic cyclophosphamide-induced overactive bladder model in mice","volume":"30","author":"Boudes","year":"2011","journal-title":"Neurourol. Urodyn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nrn2401","article-title":"The neural control of micturition","volume":"9","author":"Fowler","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1136\/jnnp.2008.159178","article-title":"A UK consensus on the management of the bladder in multiple sclerosis","volume":"85","author":"Fowler","year":"2009","journal-title":"Postgrad. Med. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1007\/s12035-018-1131-8","article-title":"The Role of the Periaqueductal Gray Matter in Lower Urinary Tract Function","volume":"56","author":"Zare","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S95","DOI":"10.5213\/inj.1632712.356","article-title":"Pathomechanism of Interstitial Cystitis\/Bladder Pain Syndrome and Mapping the Heterogeneity of Disease","volume":"20","author":"Jhang","year":"2016","journal-title":"Int. Neurourol. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E143","DOI":"10.1152\/ajpendo.00304.2023","article-title":"The role of orosomucoid in glucose and lipid metabolism and metabolic diseases","volume":"330","author":"Zhang","year":"2026","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/iju.12370","article-title":"Inflammation characteristics in bladder pain syndrome ESSIC type 3C\/classic interstitial cystitis","volume":"21","author":"Logadottir","year":"2014","journal-title":"Int. J. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wu, Y.H., Chueh, K.S., Chuang, S.M., Long, C.Y., Lu, J.H., and Juan, Y.S. (2021). Bladder Hyperactivity Induced by Oxidative Stress and Bladder Ischemia: A Review of Treatment Strategies with Antioxidants. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116014"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1097\/01.ju.0000137844.77524.97","article-title":"Intravesical botulinum toxin a administration produces analgesia against acetic acid induced bladder pain responses in rats","volume":"172","author":"Chuang","year":"2004","journal-title":"J. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/nau.21022","article-title":"Nerve growth factor in bladder dysfunction: Contributing factor, biomarker, and therapeutic target","volume":"30","author":"Ochodnicky","year":"2011","journal-title":"Neurourol. Urodyn."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1002\/nau.23210","article-title":"Could urinary nerve growth factor be a biomarker for overactive bladder? A meta-analysis","volume":"36","author":"Sheng","year":"2017","journal-title":"Neurourol. Urodyn."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12031-018-1170-7","article-title":"PACAP\/PAC1 Expression and Function in Micturition Pathways","volume":"68","author":"Ojala","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ke, H., Zhu, L., Zhang, W., Wang, H., Ding, Z., Su, D., Wang, Q., and Xu, K. (2024). PACAP\/PAC1 regulation in cystitis rats: Induction of bladder inflammation cascade leading to bladder dysfunction. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1413078"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.tips.2006.07.002","article-title":"Rho kinase: A target for treating urinary bladder dysfunction?","volume":"27","author":"Peters","year":"2006","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s00210-017-1361-8","article-title":"Rho kinase inhibition ameliorates cyclophosphamide-induced cystitis in rats","volume":"390","author":"Wrobel","year":"2017","journal-title":"Naunyn. Schmiedebergs Arch. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0304-3940(97)00284-X","article-title":"NGF and BDNF increase the immunoreactivity of vesicular acetylcholine transporter in cultured neurons from the embryonic rat septum","volume":"226","author":"Takei","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1042\/BJ20121662","article-title":"Regulation of cholinergic activity by the vesicular acetylcholine transporter","volume":"450","author":"Prado","year":"2013","journal-title":"Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1016\/j.lfs.2007.02.010","article-title":"Non-neuronal acetylcholine and urinary bladder urothelium","volume":"80","author":"Beckel","year":"2007","journal-title":"Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.expneurol.2010.05.012","article-title":"Experimental colitis triggers the release of substance P and calcitonin gene-related peptide in the urinary bladder via TRPV1 signaling pathways","volume":"225","author":"Pan","year":"2010","journal-title":"Exp. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1152\/physrev.00034.2013","article-title":"Calcitonin gene-related peptide: Physiology and pathophysiology","volume":"94","author":"Russell","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0006-8993(99)01371-2","article-title":"Organization of the secretory machinery in the rodent brain: Distribution of the t-SNAREs, SNAP-25 and SNAP-23","volume":"831","author":"Chen","year":"1999","journal-title":"Brain Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Liu, H.T., Chen, S.H., Chancellor, M.B., and Kuo, H.C. (2015). Presence of Cleaved Synaptosomal-Associated Protein-25 and Decrease of Purinergic Receptors P2X3 in the Bladder Urothelium Influence Efficacy of Botulinum Toxin Treatment for Overactive Bladder Syndrome. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134803"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"F305","DOI":"10.1152\/ajprenal.00341.2003","article-title":"Distribution of the tight junction proteins ZO-1, occludin, and claudin-4, -8, and -12 in bladder epithelium","volume":"287","author":"Acharya","year":"2004","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_41","first-page":"1103","article-title":"Participation of TNF-alpha and IL-1 in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis","volume":"28","author":"Gomes","year":"1995","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Aizawa, N., Natsuya, H., and Fujita, T. (2024). Changes of the Urothelial Barrier System in the Cyclophosphamide-Induced Cystitis in Rats by Using a Newly Established \"Inside-Out\" Urinary Bladder Preparation. Low. Urin. Tract. Symptoms, 16.","DOI":"10.1111\/luts.12538"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1172\/JCI119230","article-title":"Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder","volume":"99","author":"Freeman","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Zhang, C.O., Li, Z.L., and Kong, C.Z. (2005). APF, HB-EGF, and EGF biomarkers in patients with ulcerative vs. non-ulcerative interstitial cystitis. BMC Urol., 5.","DOI":"10.1186\/1471-2490-5-7"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0022-5347(01)61998-0","article-title":"Alteration of the insulin-like growth factor system of mitogens in hyperplastic bladders of paraplegic rats","volume":"161","author":"Elhilali","year":"1999","journal-title":"J. Urol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0022-5347(05)65005-7","article-title":"A comparison of multiple urine markers for interstitial cystitis","volume":"167","author":"Erickson","year":"2002","journal-title":"J. Urol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1007\/s00192-016-3027-3","article-title":"Fourteen-day administration of corticosterone may induce detrusor overactivity symptoms","volume":"27","author":"Wrobel","year":"2016","journal-title":"Int. Urogynecol. J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ji, N., Pan, S., Shao, C., Chen, Y., Zhang, Z., Wang, R., Qiu, Y., Jin, M., and Kong, D. (2018). Spinacetin Suppresses the Mast Cell Activation and Passive Cutaneous Anaphylaxis in Mouse Model. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00824"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.vascn.2015.04.006","article-title":"A new model of detrusor overactivity in conscious rats induced by retinyl acetate instillation","volume":"74","author":"Wrobel","year":"2015","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Juszczak, K., Adamowicz, J., Zapala, L., Kluz, T., Adamczyk, P., Wdowiak, A., Bojar, I., Misiek, M., Grzybowska, M.E., and Stangel-Wojcikiewicz, K. (2022). Potentilla chinensis aqueous extract attenuates cyclophosphamide-induced hemorrhagic cystitis in rat model. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-17393-8"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1002\/nau.23973","article-title":"Intravesical administration of blebbistatin prevents cyclophosphamide-induced toxicity of the urinary bladder in female Wistar rats","volume":"38","author":"Wrobel","year":"2019","journal-title":"Neurourol. Urodyn."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"13","DOI":"10.5213\/inj.2012.16.1.13","article-title":"Effects of Tamsulosin on Urinary Bladder Function and Neuronal Activity in the Voiding Centers of Rats with Cyclophosphamide-induced Overactive Bladder","volume":"16","author":"Kim","year":"2012","journal-title":"Int. Neurourol. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3056\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:47:54Z","timestamp":1774615674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/7\/3056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27073056"],"URL":"https:\/\/doi.org\/10.3390\/ijms27073056","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]}}}