MP63-12 AN INVESTIGATIVE STUDY ON DRUG DISCOVERY UTILIZING THE CRYSTAL PHAGOCYTIC ABILITY OF MACROPHAGES THROUGH THE ANALYSIS OF AN FDA-APPROVED DRUG LIBRARY
Atsushi Okada, Hiroshi Takase, Rei Unno, Kazumi Taguchi, Kazuhiro Niimi, Shuzo Hamamoto, Ryosuke Ando, Masahito Hirose, Tadahiro Hashita, Takahiro Iwao, Tamihide Matsunaga, Kenjiro Kohri, Takahiro Yasui · The Journal of Urology · 2024
You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP63)1 May 2024MP63-12 AN INVESTIGATIVE STUDY ON DRUG DISCOVERY UTILIZING THE CRYSTAL PHAGOCYTIC ABILITY OF MACROPHAGES THROUGH THE ANALYSIS OF AN FDA-APPROVED DRUG LIBRARY Atsushi Okada, Hiroshi Takase, Rei Unno, Kazumi Taguchi, Kazuhiro Niimi, Shuzo Hamamoto, Ryosuke Ando, Masahito Hirose, Tadahiro Hashita, Takahiro Iwao, Tamihide Matsunaga, Kenjiro Kohri, and Takahiro Yasui Atsushi OkadaAtsushi Okada , Hiroshi TakaseHiroshi Takase , Rei UnnoRei Unno , Kazumi TaguchiKazumi Taguchi , Kazuhiro NiimiKazuhiro Niimi , Shuzo HamamotoShuzo Hamamoto , Ryosuke AndoRyosuke Ando , Masahito HiroseMasahito Hirose , Tadahiro HashitaTadahiro Hashita , Takahiro IwaoTakahiro Iwao , Tamihide MatsunagaTamihide Matsunaga , Kenjiro KohriKenjiro Kohri , and Takahiro YasuiTakahiro Yasui View All Author Informationhttps://doi.org/10.1097/01.JU.0001009436.52988.91.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We have reported that the phagocytosis of calcium oxalate monohydrate (COM) crystals by macrophages (Mφ) serves as a crucial defensive factor against urinary stones. Furthermore, we have indicated the potential impairment of this factor in patients with urinary stones. To explore potential therapeutics capitalizing on this mechanism, we conducted crystal phagocytosis assays using an FDA-approved drug library. METHODS: From the FDA-approved Drug Library, we selected 1,673 drugs that are retrievable using the keywords 'Kidney stone', 'Urinary stone', 'Urolithiasis', and 'Macrophage' on PubMed. Cultured Mφ RAW267.4 cells were stained with CellTracker™ Orange CMRA Dye and adjusted to 1x104 cells/100 µL, which were then aliquoted 100 µL per well in a 96-well plate. Each well received a 10 µM dose of the respective drug, followed by the addition of Alexa Fluor 488 stained fluorescent COM crystals at 15 µg/cm2. Using the IncuCyte® high-throughput live-cell analysis system, we measured the cell area and COM area, calculating the total COM remaining amount (CRA). RESULTS: Ive imaging confirmed Mφ phagocytosing the crystals while extending its dendrites. We conducted experiments for all drugs 3-5 times and selected 116 drugs that significantly lowered the CRA value than the solvent DMSO, and then tested them 30-40 times under the same conditions and we selected 22 types of drugs. CONCLUSIONS: We identified a group of FDA-approved drugs that significantly alter the phagocytosis of COM crystals. Future studies using human Mφ models, animal model research, and clinical trials will validate their therapeutic efficacy against urinary stones. Download PPTDownload PPT Source of Funding: Grants-in-Aid for Scientific Research (B) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1035 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Atsushi Okada More articles by this author Hiroshi Takase More articles by this author Rei Unno More articles by this author Kazumi Taguchi More articles by this author Kazuhiro Niimi More articles by this author Shuzo Hamamoto More articles by this author Ryosuke Ando More articles by this author Masahito Hirose More articles by this author Tadahiro Hashita More articles by this author Takahiro Iwao More articles by this author Tamihide Matsunaga More articles by this author Kenjiro Kohri More articles by this author Takahiro Yasui More articles by this author Expand All Advertisement PDF downloadLoading ...