Mp21-11 Vincristine Treatment During Childhood Induced Histamine-Sensitive Detrusor Overactivity, a Murine Study

You have accessJournal of UrologyPediatrics II (MP21)1 May 2024MP21-11 VINCRISTINE TREATMENT DURING CHILDHOOD INDUCED HISTAMINE-SENSITIVE DETRUSOR OVERACTIVITY, A MURINE STUDY Ali Teimouri, Nao Iguchi, Duncan Wilcox, Anna Malykhina, and Nicholas G. Cost Ali TeimouriAli Teimouri , Nao IguchiNao Iguchi , Duncan WilcoxDuncan Wilcox , Anna MalykhinaAnna Malykhina , and Nicholas G. CostNicholas G. Cost View All Author Informationhttps://doi.org/10.1097/01.JU.0001008844.84871.17.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Advancements in childhood cancer treatment have led to a shift in focus to investigating the long-term impact of curative therapies on survivors. There has been a paucity of studies into the effects of chemotherapeutic drugs on bladder function. Vincristine (VCR) is one of the most common chemotherapy agents used in pediatric cancer treatment, however, it is well known to cause peripheral neuropathy. Our recent study demonstrated a higher rate of LUT dysfunction (LUTD) in childhood cancer survivors who received VCR and/or doxorubicin than a control cohort, warranting further investigation. The current study aims to investigate the impact of systemic VCR exposure on LUT function using a juvenile murine model. METHODS: With IACUC approval, juvenile male CD-1 mice received an intraperitoneal injection of 750 µg/kg of VCR twice per week for 4 weeks. Five weeks after the last treatment, impacts on the bladder were evaluated by histology, physiological recordings using bladder strips, and gene expression analysis by qPCR. RESULTS: VCR exposure induced an accumulation of mast cells in the bladder compared to the control group (8.0±1.4 vs. 3.0±0.4 cells/mm2, p=0.0014). The nerve-mediated contractile responses (EFS) in the bladder strips from the VCR group were significantly impaired compared to a control group (0.29±0.03 vs. 0.44±0.03 g/mg, p=0.002). Histamine induced a 2.8-fold larger contractile force (p=0.004) as well as a 12-fold higher increase in the basal tone (p<0.001) in the bladder strips from mice who received VCR compared to the control group. The expression levels of histamine receptors, (Hhr1, Hhr2, and Hhr3) were increased by 2.1- to 3.5-fold in the bladders from VCR treated mice compared to the control mice although the changes were not statistically significant (p>0.05). CONCLUSIONS: Systemic VCR exposure affected neuromuscular mechanisms necessary for normal LUT function, seemingly related to inflammatory responses and an increased histamine sensitivity in the detrusor muscle in juvenile mice. Our results suggest VCR therapy be studied further as a risk factor for LUTD in childhood cancer survivors. We also suggest follow-up urological assessment for these patients who receive VCR. Download PPT Source of Funding: NIH K23 (1K23DK125673-01, NC), CCTSI (KL2TR001080, NC), University of Colorado SOM AEF (NC), Ponzio Family Endowment Fund (NC & DW) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e333 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Ali Teimouri More articles by this author Nao Iguchi More articles by this author Duncan Wilcox More articles by this author Anna Malykhina More articles by this author Nicholas G. Cost More articles by this author Expand All Advertisement PDF downloadLoading ...