{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:00:52Z","timestamp":1785891652383,"version":"3.56.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2025,2]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Oxatomide, an antihistamine drug of the diphenylmethylpiperazine family, has anti\u2010inflammatory effects in airway disease. Because oxatomide was shown to cause diverse physiological responses in several cell models, the impact of oxatomide on Ca\n 2+<\/jats:sup>\n signaling and its related physiological effects has not been explored in IMR\u201090 human fetal lung fibroblasts.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n \n This study assessed the effect of oxatomide on cell viability and intracellular free Ca\n 2+<\/jats:sup>\n concentrations ([Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n ) and examined whether oxatomide\u2010induced cytotoxicity through Ca\n 2+<\/jats:sup>\n signaling in IMR\u201090 cells.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Cell viability was measured by the cell proliferation reagent (WST\u20101). [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n was measured by the Ca\n 2+<\/jats:sup>\n \u2010sensitive fluorescent dye fura\u20102.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Oxatomide (10\u201340\u2009\u03bcM) concentration dependently reduced cell viability and induced [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n rises in IMR\u201090 cells. This cytotoxic effect was reversed by chelation of cytosolic Ca\n 2+<\/jats:sup>\n with BAPTA\u2010AM. In terms of Ca\n 2+<\/jats:sup>\n signaling, oxatomide\u2010caused Ca\n 2+<\/jats:sup>\n entry was inhibited by modulators of store\u2010operated Ca\n 2+<\/jats:sup>\n channels (2\u2010APB and SKF96365) and protein kinase C (PKC) inhibitor (GF109203X). Furthermore, oxatomide\u2010induced Ca\n 2+<\/jats:sup>\n influx was confirmed by Mn\n 2+<\/jats:sup>\n \u2010induced quench of fura\u20102 fluorescence. In a Ca\n 2+<\/jats:sup>\n \u2010free medium, preincubation with the endoplasmic reticulum Ca\n 2+<\/jats:sup>\n pump inhibitor thapsigargin inhibited oxatomide\u2010evoked [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n rises. Conversely, treatment with oxatomide abolished thapsigargin\u2010induced [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n rises. Inhibition of phospholipase C (PLC) with U73122 also inhibited oxatomide\u2010caused [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n rises.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n In IMR\u201090 cells, oxatomide\u2010induced cytotoxicity by preceding [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n rises involving PKC\u2010sensitive store\u2010operated Ca\n 2+<\/jats:sup>\n entry and PLC\u2010dependent Ca\n 2+<\/jats:sup>\n release from the endoplasmic reticulum. BAPTA\u2010AM, with its Ca\n 2+<\/jats:sup>\n chelating effects, may be a potential compound for preventing oxatomide\u2010induced cytotoxicity.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/fcp.13040","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T08:04:24Z","timestamp":1729497864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Induction of Ca\n 2+<\/sup>\n signaling and cytotoxic responses of human lung fibroblasts upon an antihistamine drug oxatomide treatment and evaluating the protective effects of Ca\n 2+<\/sup>\n chelating"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-6377","authenticated-orcid":false,"given":"Wei\u2010Zhe","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Master Program, College of Pharmacy and Health Care Tajen University Yanpu Township Pingtung County Taiwan"},{"name":"Department of Medical Education and Research Kaohsiung Veterans General Hospital Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai\u2010Wei","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Kaohsiung Veterans General Hospital Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zong\u2010Da","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Kaohsiung Veterans General Hospital Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9317-0929","authenticated-orcid":false,"given":"Gwo\u2010Ching","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Kaohsiung Veterans General Hospital Kaohsiung Taiwan"},{"name":"Department of Anesthesiology Tri\u2010Service General Hospital and National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"e_1_2_12_2_1","article-title":"Oxatomide for stable asthma in adults and children","volume":"2","author":"Hayashi K","year":"2003","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000341637"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.136"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.328"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000234655"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00169216"},{"issue":"4","key":"e_1_2_12_8_1","first-page":"207","article-title":"Antiinflammatory effects of oxatomide","volume":"9","author":"Marone G","year":"1999","journal-title":"J Invest Allergol Clin 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