{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:06:46Z","timestamp":1790024806969,"version":"4.0.1"},"reference-count":27,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T00:00:00Z","timestamp":1737849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea","award":["NRF-2021R1I1A3040332"],"award-info":[{"award-number":["NRF-2021R1I1A3040332"]}]},{"name":"National Research Foundation of Korea","award":["IRIS RS-2023-00238572"],"award-info":[{"award-number":["IRIS RS-2023-00238572"]}]},{"name":"National Research Foundation of Korea","award":["NRF-2021R1F1A1062363"],"award-info":[{"award-number":["NRF-2021R1F1A1062363"]}]},{"name":"Gyeongsang National University","award":["NRF-2021R1I1A3040332"],"award-info":[{"award-number":["NRF-2021R1I1A3040332"]}]},{"name":"Gyeongsang National University","award":["IRIS RS-2023-00238572"],"award-info":[{"award-number":["IRIS RS-2023-00238572"]}]},{"name":"Gyeongsang National University","award":["NRF-2021R1F1A1062363"],"award-info":[{"award-number":["NRF-2021R1F1A1062363"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lipid emulsion has recently emerged as an effective agent for improving the cardiotoxicity of highly lipophilic drugs. However, its effect on cardiotoxicity induced by labetalol, a nonselective beta-blocker, remains unknown. In this study, we investigated the effects of lipid emulsion on the cardiotoxicity of labetalol in rat cardiomyoblasts and tried to decipher the underlying mechanisms. The effects of lipid emulsion on labetalol-induced changes in cell viability, expression of Bax\/Bcl-2, cleaved caspase-3, and cleaved caspase-9, and phosphorylation of GSK-3\u03b2, Akt, and PI3K were examined. Lipid emulsion inhibited labetalol-induced decrease in cell viability, whereas LY294002, MK2206, and SB216763, the inhibitors of phosphoinositide 3-kinase (PI3K), Akt, glycogen synthase kinase-3\u03b2 (GSK-3\u03b2), respectively, partially attenuated this restoration of cell viability. Lipid emulsion reversed the increase in expression of cleaved caspase-3, cleaved caspase-9, and Bax\/Bcl-2 and decrease in the phosphorylation of GSK-3\u03b2, Akt, and PI3K by labetalol. Lipid emulsion and cyclosporin, a mitochondrial permeability transition pore (MPTP) inhibitor, reduced the labetalol-induced increase in the number of TUNEL-positive cells and promoted late-stage apoptosis. Overall, lipid emulsion inhibited apoptotic cell death caused by labetalol toxicity via the inhibition of intrinsic apoptotic pathway and MPTP in rat cardiomyoblasts, which appears to involve PI3K, Akt, and GSK-3\u03b2 signaling pathways.<\/jats:p>","DOI":"10.3390\/cells14030187","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T04:59:10Z","timestamp":1737953950000},"page":"187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lipid Emulsion Mitigates the Cardiotoxic Effects of Labetalol in Rat Cardiomyoblasts"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-0180","authenticated-orcid":false,"given":"Gyujin","family":"Sim","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju-si 52727, Republic of Korea"},{"name":"Institute of Medical Science, Gyeongsang National University, Jinju-si 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1292-7108","authenticated-orcid":false,"given":"Seong-Ho","family":"Ok","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Gyeongsang National University, Jinju-si 52727, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon-si 51472, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Jinju-si 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-633X","authenticated-orcid":false,"given":"Soo Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Gyeongsang National University, Jinju-si 52727, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon-si 51472, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Jinju-si 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong-Eon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, Jinju-si 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunghyeon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju-si 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0102-5800","authenticated-orcid":false,"given":"Ju-Tae","family":"Sohn","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Gyeongsang National University, Jinju-si 52727, Republic of Korea"},{"name":"Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, Jinju-si 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/j.1875-9114.1983.tb03252.x","article-title":"Labetalol: A review of its pharmacology, pharmacokinetics, clinical uses and adverse effects","volume":"3","author":"MacCarthy","year":"1983","journal-title":"Pharmacotherapy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.emc.2007.02.001","article-title":"2nd. 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