{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T21:16:05Z","timestamp":1785791765333,"version":"3.56.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["819531"],"award-info":[{"award-number":["819531"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["101082064"],"award-info":[{"award-number":["101082064"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medizinische Hochschule Hannover (MHH)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n                <jats:title>Abstract<\/jats:title>\n                <jats:p>Cisplatin is a chemotherapeutic agent widely used to treat solid tumors. However, it can also be highly ototoxic, resulting in high-frequency hearing loss. Cisplatin causes degeneration of hair cells (HCs) and spiral ganglion neurons (SGNs) in the inner ear, which are essential components of the hearing process and cannot be regenerated in mammals. As the affected cells primarily die by apoptosis, we tested several anti-apoptotic small molecules to protect these cells from drug-induced toxicity. We found that the general caspase inhibitor Emricasan could significantly counteract the toxic effects of cisplatin in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, phoenix auditory cells, and primary SGNs. Importantly, the anti-cytotoxic effect in neuronal cells was even more pronounced than the effect of sodium thiosulfate (STS), which is currently the only approved prevention option for cisplatin-induced ototoxicity. Finally, we tested the protective effect of Emricasan treatment in the context of another ototoxic drug, i.e., the aminoglycoside antibiotic neomycin, and again found a significant increase in cell viability when the cultures were co-treated with Emricasan. These results suggest a promising strategy to prevent ototoxicity in patients by temporarily blocking the apoptotic pathway when applying cisplatin or aminoglycoside antibiotics.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Key messages<\/jats:title>\n                <jats:p><jats:list list-type=\"bullet\">\n                  <jats:list-item>\n                    <jats:p>Anti-apoptotic small molecules can reduce cisplatin-induced toxicity.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Emricasan can effectively exert its anti-apoptotic effect on cochlear cells.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Strong protection from cisplatin- and neomycin-induced cytotoxicity with Emricasan.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Sodium thiosulfate and Emricasan provide similar protective effects to cisplatin-treated cells.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Emricasan is more potent than sodium thiosulfate in reducing neomycin-induced cytotoxicity.<\/jats:p>\n                  <\/jats:list-item>\n                <\/jats:list><\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00109-024-02472-2","type":"journal-article","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T06:17:20Z","timestamp":1723011440000},"page":"1163-1174","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The caspase-inhibitor Emricasan efficiently counteracts cisplatin- and neomycin-induced cytotoxicity in cochlear cells"],"prefix":"10.1007","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3430-6110","authenticated-orcid":false,"given":"Larissa","family":"Nassauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9583-6757","authenticated-orcid":false,"given":"Juliane W.","family":"Schott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2645-8135","authenticated-orcid":false,"given":"Jennifer","family":"Harre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9652-1035","authenticated-orcid":false,"given":"Athanasia","family":"Warnecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-2180","authenticated-orcid":false,"given":"Michael","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1778-983X","authenticated-orcid":false,"given":"Melanie","family":"Galla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2743-0070","authenticated-orcid":false,"given":"Axel","family":"Schambach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,8,7]]},"reference":[{"key":"2472_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1749-6632.1999.tb00277.x","volume":"884","author":"E Arslan","year":"1999","unstructured":"Arslan E, Orzan E, Santarelli R (1999) Global problem of drug-induced hearing loss. Ann NY Acad Sci 884:1\u201314. https:\/\/doi.org\/10.1111\/j.1749-6632.1999.tb00277.x","journal-title":"Ann NY Acad Sci"},{"key":"2472_CR2","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1002\/cpt.603","volume":"101","author":"C Lanvers-Kaminsky","year":"2017","unstructured":"Lanvers-Kaminsky C, Am Z-D, Parfitt R, Ciarimboli G (2017) Drug-induced ototoxicity: mechanisms, pharmacogenetics, and protective strategies. Clin Pharmacol Ther 101:491\u2013500. https:\/\/doi.org\/10.1002\/cpt.603","journal-title":"Clin Pharmacol Ther"},{"key":"2472_CR3","first-page":"559","volume":"18","author":"RD Kopke","year":"1997","unstructured":"Kopke RD, Liu W, Gabaizadeh R et al (1997) Use of organotypic cultures of Corti\u2019s organ to study the protective effects of antioxidant molecules on cisplatin-induced damage of auditory hair cells. Am J Otol 18:559\u2013571","journal-title":"Am J Otol"},{"key":"2472_CR4","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.1002\/ar.22578","volume":"295","author":"J Schacht","year":"2012","unstructured":"Schacht J, Talaska AE, Rybak LP (2012) Cisplatin and aminoglycoside antibiotics: hearing loss and its prevention. Anat Rec (Hoboken) 295:1837\u20131850. https:\/\/doi.org\/10.1002\/ar.22578","journal-title":"Anat Rec (Hoboken)"},{"key":"2472_CR5","doi-asserted-by":"publisher","first-page":"9960","DOI":"10.1093\/nar\/gky833","volume":"46","author":"M Kulik","year":"2018","unstructured":"Kulik M, Mori T, Sugita Y, Trylska J (2018) Molecular mechanisms for dynamic regulation of N1 riboswitch by aminoglycosides. Nucleic Acids Res 46:9960\u20139970. https:\/\/doi.org\/10.1093\/nar\/gky833","journal-title":"Nucleic Acids Res"},{"key":"2472_CR6","first-page":"97","volume":"11","author":"A Brown","year":"2019","unstructured":"Brown A, Kumar S, Tchounwou PB (2019) Cisplatin-based chemotherapy of human cancers. J Cancer Sci Ther 11:97","journal-title":"J Cancer Sci Ther"},{"key":"2472_CR7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.7874\/jao.2017.00360","volume":"22","author":"P Ganesan","year":"2018","unstructured":"Ganesan P, Schmiedge J, Manchaiah V et al (2018) Ototoxicity: a challenge in diagnosis and treatment. J Audiol Otol 22:59\u201368. https:\/\/doi.org\/10.7874\/jao.2017.00360","journal-title":"J Audiol Otol"},{"key":"2472_CR8","first-page":"601","volume":"15","author":"G Cianfrone","year":"2011","unstructured":"Cianfrone G, Pentangelo D, Cianfrone F et al (2011) Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide. Eur Rev Med Pharmacol Sci 15:601\u2013636","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2472_CR9","doi-asserted-by":"publisher","first-page":"448","DOI":"10.3109\/00016489.2013.879740","volume":"134","author":"P Dammeyer","year":"2014","unstructured":"Dammeyer P, Hellberg V, Wallin I et al (2014) Cisplatin and oxaliplatin are toxic to cochlear outer hair cells and both target thioredoxin reductase in organ of Corti cultures. Acta Otolaryngol 134:448\u2013454. https:\/\/doi.org\/10.3109\/00016489.2013.879740","journal-title":"Acta Otolaryngol"},{"key":"2472_CR10","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.heares.2008.01.013","volume":"239","author":"OW Guthrie","year":"2008","unstructured":"Guthrie OW, Li-Korotky HS, Durrant JD, Balaban C (2008) Cisplatin induces cytoplasmic to nuclear translocation of nucleotide excision repair factors among spiral ganglion neurons. Hear Res 239:79\u201391. https:\/\/doi.org\/10.1016\/j.heares.2008.01.013","journal-title":"Hear Res"},{"key":"2472_CR11","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1023\/a:1015434524040","volume":"26","author":"HC Dodson","year":"1997","unstructured":"Dodson HC (1997) Loss and survival of spiral ganglion neurons in the guinea pig after intracochlear perfusion with aminoglycosides. J Neurocytol 26:541\u2013556. https:\/\/doi.org\/10.1023\/a:1015434524040","journal-title":"J Neurocytol"},{"key":"2472_CR12","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/BF00302950","volume":"195","author":"HF Schuknecht","year":"1970","unstructured":"Schuknecht HF, Montandon P (1970) Pathology of the ear in pneumococcal meningitis. Arch Klin Exp Ohren Nasen Kehlkopfheilkd 195:207\u2013225. https:\/\/doi.org\/10.1007\/BF00302950","journal-title":"Arch Klin Exp Ohren Nasen Kehlkopfheilkd"},{"key":"2472_CR13","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.3109\/10715762.2011.591391","volume":"45","author":"T Itoh","year":"2011","unstructured":"Itoh T, Terazawa R, Kojima K et al (2011) Cisplatin induces production of reactive oxygen species via NADPH oxidase activation in human prostate cancer cells. Free Radic Res 45:1033\u20131039. https:\/\/doi.org\/10.3109\/10715762.2011.591391","journal-title":"Free Radic Res"},{"key":"2472_CR14","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1007\/s10495-007-0082-8","volume":"12","author":"P Bragado","year":"2007","unstructured":"Bragado P, Armesilla A, Silva A, Porras A (2007) Apoptosis by cisplatin requires p53 mediated p38\u03b1 MAPK activation through ROS generation. Apoptosis 12:1733\u20131742. https:\/\/doi.org\/10.1007\/s10495-007-0082-8","journal-title":"Apoptosis"},{"key":"2472_CR15","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1016\/j.freeradbiomed.2011.07.015","volume":"51","author":"S Denamur","year":"2011","unstructured":"Denamur S, Tyteca D, Marchand-Brynaert J et al (2011) Role of oxidative stress in lysosomal membrane permeabilization and apoptosis induced by gentamicin, an aminoglycoside antibiotic. Free Radic Biol Med 51:1656\u20131665. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2011.07.015","journal-title":"Free Radic Biol Med"},{"key":"2472_CR16","doi-asserted-by":"publisher","first-page":"70","DOI":"10.9790\/0853-14117077","volume":"14","author":"DD Nwibo","year":"2015","unstructured":"Nwibo DD, Levi CA, Nwibo MI (2015) Small molecule drugs; down but not out: a future for medical research and therapeutics. IOSR Dent Med Sci 14:70\u201377. https:\/\/doi.org\/10.9790\/0853-14117077","journal-title":"IOSR Dent Med Sci"},{"key":"2472_CR17","doi-asserted-by":"publisher","first-page":"2376","DOI":"10.1056\/nejmoa1801109","volume":"378","author":"PR Brock","year":"2018","unstructured":"Brock PR, Maibach R, Childs M et al (2018) Sodium thiosulfate for protection from cisplatin-induced hearing loss. N Engl J Med 378:2376\u20132385. https:\/\/doi.org\/10.1056\/nejmoa1801109","journal-title":"N Engl J Med"},{"key":"2472_CR18","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1097\/00129492-200411000-00009","volume":"25","author":"W-T Choe","year":"2004","unstructured":"Choe W-T, Chinosornvatana N, Chang KW (2004) Prevention of cisplatin ototoxicity using transtympanic N-acetylcysteine and lactate. Otol Neurotol 25:910\u2013915. https:\/\/doi.org\/10.1097\/00129492-200411000-00009","journal-title":"Otol Neurotol"},{"key":"2472_CR19","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1017\/S0022215116000992","volume":"130","author":"I Aladag","year":"2016","unstructured":"Aladag I, Guven M, Songu M (2016) Prevention of gentamicin ototoxicity with N-acetylcysteine and vitamin A. J Laryngol Otol 130:440\u2013446. https:\/\/doi.org\/10.1017\/S0022215116000992","journal-title":"J Laryngol Otol"},{"key":"2472_CR20","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1097\/MAO.0b013e31818599d5","volume":"29","author":"GW Hill","year":"2008","unstructured":"Hill GW, Morest DK, Parham K (2008) Cisplatin-induced ototoxicity: effect of intratympanic dexamethasone injections. Otol Neurotol 29:1005\u20131011. https:\/\/doi.org\/10.1097\/MAO.0b013e31818599d5","journal-title":"Otol Neurotol"},{"key":"2472_CR21","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1177\/0194599811406673","volume":"145","author":"D Murphy","year":"2011","unstructured":"Murphy D, Daniel SJ (2011) Intratympanic dexamethasone to prevent cisplatin ototoxicity: a guinea pig model. Otolaryngol Head Neck Surg 145:452\u2013457. https:\/\/doi.org\/10.1177\/0194599811406673","journal-title":"Otolaryngol Head Neck Surg"},{"key":"2472_CR22","doi-asserted-by":"publisher","first-page":"9217","DOI":"10.1158\/0008-5472.CAN-04-1581","volume":"64","author":"J Wang","year":"2004","unstructured":"Wang J, Ladrech S, Pujol R et al (2004) Caspase inhibitors, but not c-Jun NH 2-terminal kinase inhibitor treatment, prevent cisplatin-induced hearing loss. Cancer Res 64:9217\u20139224. https:\/\/doi.org\/10.1158\/0008-5472.CAN-04-1581","journal-title":"Cancer Res"},{"key":"2472_CR23","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.anl.2004.11.006","volume":"32","author":"T Okuda","year":"2005","unstructured":"Okuda T, Sugahara K, Takemoto T et al (2005) Inhibition of caspases alleviates gentamicin-induced cochlear damage in guinea pigs. Auris Nasus Larynx 32:33\u201337. https:\/\/doi.org\/10.1016\/j.anl.2004.11.006","journal-title":"Auris Nasus Larynx"},{"key":"2472_CR24","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S0306-4522(03)00286-0","volume":"120","author":"M Zhang","year":"2003","unstructured":"Zhang M, Liu W, Ding D, Salvi R (2003) Pifithrin-\u03b1 supresses p53 and protects cochlear and vestibular hair cells from cisplatin-induced apoptosis. Neuroscience 120:191\u2013205. https:\/\/doi.org\/10.1016\/S0306-4522(03)00286-0","journal-title":"Neuroscience"},{"key":"2472_CR25","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.taap.2016.08.020","volume":"309","author":"S Denamur","year":"2016","unstructured":"Denamur S, Boland L, Beyaert M et al (2016) Subcellular mechanisms involved in apoptosis induced by aminoglycoside antibiotics: Insights on p53, proteasome and endoplasmic reticulum. Toxicol Appl Pharmacol 309:24\u201336. https:\/\/doi.org\/10.1016\/j.taap.2016.08.020","journal-title":"Toxicol Appl Pharmacol"},{"key":"2472_CR26","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/S1470-2045(16)30625-8","volume":"18","author":"DR Freyer","year":"2017","unstructured":"Freyer DR, Chen L, Krailo MD et al (2017) Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol 18:63\u201374. https:\/\/doi.org\/10.1016\/S1470-2045(16)30625-8","journal-title":"Lancet Oncol"},{"key":"2472_CR27","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1007\/BF00257119","volume":"13","author":"J Uozumi","year":"1984","unstructured":"Uozumi J, Ishizawa M, Lwamoto Y, Baba T (1984) Sodium thiosulfate inhibits cis-diamminedichloroplatinum (II) activity. Cancer Chemother Pharmacol 13:82\u201385. https:\/\/doi.org\/10.1007\/BF00257119","journal-title":"Cancer Chemother Pharmacol"},{"key":"2472_CR28","doi-asserted-by":"publisher","first-page":"102157","DOI":"10.1016\/j.omtn.2024.102157","volume":"35","author":"L Nassauer","year":"2024","unstructured":"Nassauer L, Staecker H, Huang P et al (2024) Protection from cisplatin-induced hearing loss with lentiviral vector-mediated ectopic expression of the anti-apoptotic protein BCL-XL. Mol Ther Nucleic Acids 35:102157. https:\/\/doi.org\/10.1016\/j.omtn.2024.102157","journal-title":"Mol Ther Nucleic Acids"},{"key":"2472_CR29","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1159\/000071059","volume":"8","author":"GM Kalinec","year":"2003","unstructured":"Kalinec GM, Webster P, Lim DJ, Kalinec F (2003) A cochlear cell line as an in vitro system for drug ototoxicity screening. Audiol Neurootol 8:177\u2013189. https:\/\/doi.org\/10.1159\/000071059","journal-title":"Audiol Neurootol"},{"key":"2472_CR30","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.heares.2016.02.019","volume":"335","author":"GM Kalinec","year":"2016","unstructured":"Kalinec GM, Thein P, Park C, Kalinec F (2016) HEI-OC1 cells as a model for investigating drug cytotoxicity. Hear Res 335:105\u2013117. https:\/\/doi.org\/10.1016\/j.heares.2016.02.019","journal-title":"Hear Res"},{"key":"2472_CR31","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/s12328-021-01585-2","volume":"15","author":"V Lekakis","year":"2022","unstructured":"Lekakis V, Cholongitas E (2022) The impact of emricasan on chronic liver diseases: current data. Clin J Gastroenterol 15:271\u2013285. https:\/\/doi.org\/10.1007\/s12328-021-01585-2","journal-title":"Clin J Gastroenterol"},{"key":"2472_CR32","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/apt.15030","volume":"49","author":"M Shiffman","year":"2019","unstructured":"Shiffman M, Freilich B, Vuppalanchi R et al (2019) Randomised clinical trial: emricasan versus placebo significantly decreases ALT and caspase 3\/7 activation in subjects with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 49:64\u201373. https:\/\/doi.org\/10.1111\/apt.15030","journal-title":"Aliment Pharmacol Ther"},{"key":"2472_CR33","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.jhep.2019.11.024","volume":"72","author":"SA Harrison","year":"2020","unstructured":"Harrison SA, Goodman Z, Jabbar A et al (2020) A randomized, placebo-controlled trial of emricasan in patients with NASH and F1\u2013F3 fibrosis. J Hepatol 72:816\u2013827. https:\/\/doi.org\/10.1016\/j.jhep.2019.11.024","journal-title":"J Hepatol"},{"key":"2472_CR34","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41420-020-00349-0","volume":"6","author":"M Jiang","year":"2020","unstructured":"Jiang M, Qi L, Li L, Li Y (2020) The caspase-3\/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer. Cell Death Discov 6:112. https:\/\/doi.org\/10.1038\/s41420-020-00349-0","journal-title":"Cell Death Discov"},{"key":"2472_CR35","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/0022-1759(95)00072-i","volume":"184","author":"I Vermes","year":"1995","unstructured":"Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C (1995) A novel assay for apoptosis Flow cytometric detection of phosphatidylserine early apoptotic cells using fluorescein labelled expression on Annexin V. J Immunol Methods 184:39\u201351. https:\/\/doi.org\/10.1016\/0022-1759(95)00072-i","journal-title":"J Immunol Methods"},{"key":"2472_CR36","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1124\/jpet.103.062034","volume":"309","author":"NC Hoglen","year":"2004","unstructured":"Hoglen NC, Chen LS, Fisher CD et al (2004) Characterization of IDN-6556 (3-{2-(2-tert-Butyl-phenylaminooxalyl)-amino]-propionylamino}-4-oxo-5-(2,3,5, 6-tetrafluoro-phenoxy)-pentanoic acid): a liver-targeted caspase inhibitor. J Pharmacol Exp Ther 309:634\u2013640. https:\/\/doi.org\/10.1124\/jpet.103.062034","journal-title":"J Pharmacol Exp Ther"},{"key":"2472_CR37","doi-asserted-by":"publisher","first-page":"108391","DOI":"10.1016\/j.heares.2021.108391","volume":"414","author":"F Rousset","year":"2022","unstructured":"Rousset F, Schmidbauer D, Fink S et al (2022) Phoenix auditory neurons as 3R cell model for high throughput screening of neurogenic compounds. Hear Res 414:108391. https:\/\/doi.org\/10.1016\/j.heares.2021.108391","journal-title":"Hear Res"},{"key":"2472_CR38","doi-asserted-by":"publisher","first-page":"395","DOI":"10.3389\/fncel.2020.599152","volume":"14","author":"F Rousset","year":"2020","unstructured":"Rousset F, Kokje VBC, Sipione R et al (2020) Intrinsically self-renewing neuroprogenitors from the A\/J mouse spiral ganglion as virtually unlimited source of mature auditory neurons. Front Cell Neurosci 14:395. https:\/\/doi.org\/10.3389\/fncel.2020.599152","journal-title":"Front Cell Neurosci"},{"key":"2472_CR39","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3342\/ceo.2011.4.2.77","volume":"4","author":"CK Lee","year":"2011","unstructured":"Lee CK, Shin JI, Cho YS (2011) Protective effect of minocycline against cisplatin-induced ototoxicity. Clin Exp Otorhinolaryngol 4:77\u201382. https:\/\/doi.org\/10.3342\/ceo.2011.4.2.77","journal-title":"Clin Exp Otorhinolaryngol"},{"key":"2472_CR40","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.heares.2004.03.012","volume":"197","author":"E Corbacella","year":"2004","unstructured":"Corbacella E, Lanzoni I, Ding D et al (2004) Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures. Hear Res 197:11\u201318. https:\/\/doi.org\/10.1016\/j.heares.2004.03.012","journal-title":"Hear Res"},{"key":"2472_CR41","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s40005-022-00586-8","volume":"53","author":"TN Nguyen","year":"2023","unstructured":"Nguyen TN, Park JS (2023) Intratympanic drug delivery systems to treat inner ear impairments. J Pharm Investig 53:93\u2013118","journal-title":"J Pharm Investig"},{"key":"2472_CR42","doi-asserted-by":"publisher","first-page":"1062379","DOI":"10.3389\/fphar.2023.1062379","volume":"14","author":"E Yildiz","year":"2023","unstructured":"Yildiz E, Gadenstaetter AJ, Gerlitz M et al (2023) Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics. Front Pharmacol 14:1062379. https:\/\/doi.org\/10.3389\/fphar.2023.1062379","journal-title":"Front Pharmacol"},{"key":"2472_CR43","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.ijpharm.2016.04.003","volume":"509","author":"M Gehrke","year":"2016","unstructured":"Gehrke M, Sircoglou J, Gnansia D et al (2016) Ear cubes for local controlled drug delivery to the inner ear. Int J Pharm 509:85\u201394. https:\/\/doi.org\/10.1016\/j.ijpharm.2016.04.003","journal-title":"Int J Pharm"},{"key":"2472_CR44","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.ijpharm.2015.04.019","volume":"487","author":"N El Kechai","year":"2015","unstructured":"El Kechai N, Bochot A, Huang N et al (2015) Effect of liposomes on rheological and syringeability properties of hyaluronic acid hydrogels intended for local injection of drugs. Int J Pharm 487:187\u2013196. https:\/\/doi.org\/10.1016\/j.ijpharm.2015.04.019","journal-title":"Int J Pharm"},{"key":"2472_CR45","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.jconrel.2013.11.021","volume":"174","author":"DA Borkholder","year":"2014","unstructured":"Borkholder DA, Zhu X, Frisina RD (2014) Round window membrane intracochlear drug delivery enhanced by induced advection. J Control Release 174:171\u2013176. https:\/\/doi.org\/10.1016\/j.jconrel.2013.11.021","journal-title":"J Control Release"},{"key":"2472_CR46","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.ijpharm.2014.05.057","volume":"471","author":"E Engleder","year":"2014","unstructured":"Engleder E, Honeder C, Klobasa J et al (2014) Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear. Int J Pharm 471:297\u2013302. https:\/\/doi.org\/10.1016\/j.ijpharm.2014.05.057","journal-title":"Int J Pharm"},{"key":"2472_CR47","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.ijpharm.2014.06.041","volume":"472","author":"AM Al-Mahallawi","year":"2014","unstructured":"Al-Mahallawi AM, Khowessah OM, Shoukri RA (2014) Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: In-vitro optimization, ex-vivo permeation studies, and in-vivo assessment. Int J Pharm 472:304\u2013314. https:\/\/doi.org\/10.1016\/j.ijpharm.2014.06.041","journal-title":"Int J Pharm"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-024-02472-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00109-024-02472-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-024-02472-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T03:43:55Z","timestamp":1724903035000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00109-024-02472-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,7]]},"references-count":47,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["2472"],"URL":"https:\/\/doi.org\/10.1007\/s00109-024-02472-2","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,7]]},"assertion":[{"value":"11 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}]}}