{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T13:43:55Z","timestamp":1793195035862,"version":"4.5.0"},"reference-count":146,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001511","name":"Auckland Medical Research Foundation (Auckland, New Zealand)","doi-asserted-by":"publisher","award":["3720285"],"award-info":[{"award-number":["3720285"]}],"id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cisplatin is a commonly used chemotherapeutic agent with proven efficacy in treating various malignancies, including testicular, ovarian, cervical, breast, bladder, head and neck, and lung cancer. Cisplatin is also used to treat tumors in children, such as neuroblastoma, osteosarcoma, and hepatoblastoma. However, its clinical use is limited by severe side effects, including ototoxicity, nephrotoxicity, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, and retinal toxicity. Cisplatin-induced ototoxicity manifests as irreversible, bilateral, high-frequency sensorineural hearing loss in 40\u201360% of adults and in up to 60% of children. Hearing loss can lead to social isolation, depression, and cognitive decline in adults, and speech and language developmental delays in children. Cisplatin causes hair cell death by forming DNA adducts, mitochondrial dysfunction, oxidative stress, and inflammation, culminating in programmed cell death by apoptosis, necroptosis, pyroptosis, or ferroptosis. Contemporary medical interventions for cisplatin ototoxicity are limited to prosthetic devices, such as hearing aids, but these have significant limitations because the cochlea remains damaged. Recently, the U.S. Food and Drug Administration (FDA) approved the first therapy, sodium thiosulfate, to prevent cisplatin-induced hearing loss in pediatric patients with localized, non-metastatic solid tumors. Other pharmacological treatments for cisplatin ototoxicity are in various stages of preclinical and clinical development. This narrative review aims to highlight the molecular mechanisms involved in cisplatin-induced ototoxicity, focusing on cochlear inflammation, and shed light on potential antioxidant and anti-inflammatory therapeutic interventions to prevent or mitigate the ototoxic effects of cisplatin. We conducted a comprehensive literature search (Google Scholar, PubMed) focusing on publications in the last five years.<\/jats:p>","DOI":"10.3390\/ijms242216545","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T10:32:32Z","timestamp":1700476352000},"page":"16545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":131,"title":["Molecular Characteristics of Cisplatin-Induced Ototoxicity and Therapeutic Interventions"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-8991","authenticated-orcid":false,"given":"Winston J. T.","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New Zealand"},{"name":"Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8548-6844","authenticated-orcid":false,"given":"Srdjan M.","family":"Vlajkovic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New Zealand"},{"name":"Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1023, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: Molecular mechanisms of action","volume":"740","author":"Dasari","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.heares.2006.09.015","article-title":"Mechanisms of cisplatin-induced ototoxicity and prevention","volume":"226","author":"Rybak","year":"2007","journal-title":"Hear. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3390\/toxics3030268","article-title":"Cisplatin-induced ototoxicity: Effects, mechanisms and protection strategies","volume":"3","author":"Callejo","year":"2015","journal-title":"Toxics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1038\/s41467-017-01837-1","article-title":"Cisplatin is retained in the cochlea indefinitely following chemotherapy","volume":"8","author":"Breglio","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3389\/fonc.2018.00363","article-title":"Vestibulotoxicity associated with platinum-based chemotherapy in survivors of cancer: A scoping review","volume":"8","author":"Prayuenyong","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"695268","DOI":"10.3389\/fnins.2021.695268","article-title":"Preferential cochleotoxicity of cisplatin","volume":"15","author":"Prayuenyong","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"999","DOI":"10.3389\/fphar.2020.00999","article-title":"Current strategies to combat cisplatin-induced ototoxicity","volume":"11","author":"Yu","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1200\/JCO.2016.66.8822","article-title":"Comprehensive audiometric analysis of hearing impairment and tinnitus after cisplatin-based chemotherapy in survivors of adult-onset cancer","volume":"34","author":"Frisina","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8588","DOI":"10.1200\/JCO.2004.00.5355","article-title":"Ototoxicity in children receiving platinum chemotherapy: Underestimating a commonly occurring toxicity that may influence academic and social development","volume":"23","author":"Knight","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_10","unstructured":"FDA (2022, October 21). FDA Approves Sodium Thiosulfate to Reduce the Risk of Ototoxicity Associated with Cisplatin in Pediatric Patients with Localized, Non-Metastatic Solid Tumors, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-sodium-thiosulfate-reduce-risk-ototoxicity-associated-cisplatin-pediatric-patients."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S1470-2045(16)30625-8","article-title":"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","volume":"18","author":"Freyer","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2376","DOI":"10.1056\/NEJMoa1801109","article-title":"Sodium thiosulfate for protection from cisplatin-induced hearing loss","volume":"378","author":"Brock","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s40272-022-00550-x","article-title":"Sodium thiosulfate: Pediatric first approval","volume":"25","author":"Dhillon","year":"2023","journal-title":"Pediatr. Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.3389\/fphys.2018.01898","article-title":"Cisplatin-membrane interactions and their influence on platinum complexes activity and toxicity","volume":"9","author":"Martinho","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1021\/acs.chemrev.5b00597","article-title":"The next generation of platinum drugs: Targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs","volume":"116","author":"Johnstone","year":"2016","journal-title":"Chem. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1021\/acs.molpharmaceut.6b00240","article-title":"Systemic delivery and biodistribution of cisplatin in vivo","volume":"13","author":"Chu","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.heares.2004.12.007","article-title":"Immunohistochemical detection of platinated DNA in the cochlea of cisplatin-treated guinea pigs","volume":"203","author":"Hendriksen","year":"2005","journal-title":"Hear. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s10162-020-00759-y","article-title":"Ototoxicity and platinum uptake following cyclic administration of platinum-based chemotherapeutic agents","volume":"21","author":"Gersten","year":"2020","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1044\/2021_AJA-21-00006","article-title":"Mechanisms of aminoglycoside- and cisplatin-induced ototoxicity","volume":"30","author":"Steyger","year":"2021","journal-title":"Am. J. Audiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14298","DOI":"10.1073\/pnas.162491399","article-title":"Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals","volume":"99","author":"Ishida","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.otc.2021.08.007","article-title":"Mechanisms of ototoxicity and otoprotection","volume":"54","author":"Steyger","year":"2021","journal-title":"Otolaryngol. Clin. N. Am."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3389\/fncel.2017.00338","article-title":"Mechanisms of cisplatin-induced ototoxicity and otoprotection","volume":"11","author":"Sheth","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9500","DOI":"10.1523\/JNEUROSCI.1544-10.2010","article-title":"Role of the copper transporter, CTR1, in platinum-induced ototoxicity","volume":"30","author":"More","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"867034","DOI":"10.3389\/fnins.2022.867034","article-title":"Supporting cells and their potential roles in cisplatin-induced ototoxicity","volume":"16","author":"Waissbluth","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"473829","DOI":"10.6064\/2012\/473829","article-title":"Membrane transporters as mediators of cisplatin effects and side effects","volume":"2012","author":"Ciarimboli","year":"2012","journal-title":"Scientifica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"jcs260590","DOI":"10.1242\/jcs.260590","article-title":"The ototoxic drug cisplatin localises to stress granules altering their dynamics and composition","volume":"136","author":"Martin","year":"2023","journal-title":"J. Cell Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.bbadis.2016.12.022","article-title":"Cytoplasmic stress granules: Dynamic modulators of cell signaling and disease","volume":"1863","author":"Mahboubi","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hofmann, S., Kedersha, N., Anderson, P., and Ivanov, P. (2021). Molecular mechanisms of stress granule assembly and disassembly. Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis., 1868.","DOI":"10.1016\/j.bbamcr.2020.118876"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1083\/jcb.200502088","article-title":"Stress granules and processing bodies are dynamically linked sites of mRNP remodeling","volume":"169","author":"Kedersha","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2731","DOI":"10.1002\/jmr.2731","article-title":"Analysis of single, cisplatin-induced DNA bends by atomic force microscopy and simulations","volume":"31","author":"Dutta","year":"2018","journal-title":"J. Mol. Recognit."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1093\/nar\/gkf405","article-title":"DNA bending and unwinding due to the major 1,2-GG intrastrand cross-link formed by antitumor cis-diamminedichloroplatinum(II) are flanking-base independent","volume":"30","author":"Stehlikova","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_32","first-page":"862879","article-title":"Mechanisms of cisplatin-induced apoptosis and of cisplatin sensitivity: Potential of BIN1 to act as a potent predictor of cisplatin sensitivity in gastric cancer treatment","volume":"2012","author":"Tanida","year":"2012","journal-title":"Int. J. Surg. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"108783","DOI":"10.1016\/j.heares.2023.108783","article-title":"Role of mitochondrial dysfunction and oxidative stress in sensorineural hearing loss","volume":"434","author":"Tan","year":"2023","journal-title":"Hear. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.heares.2013.01.006","article-title":"The mitochondrion: A perpetrator of acquired hearing loss","volume":"303","author":"Schacht","year":"2013","journal-title":"Hear. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.mito.2004.07.040","article-title":"Mitochondrial dysfunction in hearing loss","volume":"4","author":"Kopke","year":"2004","journal-title":"Mitochondrion"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kamogashira, T., Fujimoto, C., and Yamasoba, T. (2015). Reactive oxygen species, apoptosis, and mitochondrial dysfunction in hearing loss. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/617207"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.mad.2010.04.006","article-title":"Mitochondrial oxidative damage and apoptosis in age-related hearing loss","volume":"131","author":"Someya","year":"2010","journal-title":"Mech. Ageing Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"46065","DOI":"10.1074\/jbc.M403046200","article-title":"NOX3, a superoxide-generating NADPH oxidase of the inner ear","volume":"279","author":"Malgrange","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4716","DOI":"10.1523\/JNEUROSCI.2672-20.2021","article-title":"Nox3-derived superoxide in cochleae induces sensorineural hearing loss","volume":"41","author":"Mohri","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.neuroscience.2005.12.044","article-title":"Expression of the kidney injury molecule 1 in the rat cochlea and induction by cisplatin","volume":"139","author":"Mukherjea","year":"2006","journal-title":"Neuroscience"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1089\/ars.2010.3110","article-title":"Transtympanic administration of short interfering (si)RNA for the NOX3 isoform of NADPH oxidase protects against cisplatin-induced hearing loss in the rat","volume":"13","author":"Mukherjea","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.heares.2004.08.002","article-title":"Reduction of acute cisplatin ototoxicity and nephrotoxicity in rats by oral administration of allopurinol and ebselen","volume":"201","author":"Lynch","year":"2005","journal-title":"Hear. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3109\/00016489309135781","article-title":"Effects of free radicals on the intracellular calcium concentration in the isolated outer hair cell of the guinea pig cochlea","volume":"113","author":"Ikeda","year":"1993","journal-title":"Acta Otolaryngol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1055\/s-0040-1715719","article-title":"The effect of D-methionine on cochlear oxidative state with and without cisplatin administration: Mechanisms of otoprotection","volume":"14","author":"Campbell","year":"2003","journal-title":"J. Am. Acad. Audiol."},{"key":"ref_45","first-page":"513","article-title":"Effect of protective agents against cisplatin ototoxicity","volume":"21","author":"Rybak","year":"2000","journal-title":"Otol. Neurotol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1080\/00016480410017521","article-title":"Role of reactive radicals in degeneration of the auditory system of mice following cisplatin treatment","volume":"124","author":"Lee","year":"2004","journal-title":"Acta Otolaryngol."},{"key":"ref_47","first-page":"4081","article-title":"Nuclear-factor kappa B (NF-kappa B)-inducible nitric oxide synthase (iNOS\/NOS II) pathway damages the stria vascularis in cisplatin-treated mice","volume":"22","author":"Watanabe","year":"2002","journal-title":"Anticancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"18674","DOI":"10.1074\/jbc.M111.297960","article-title":"Cisplatin-induced ototoxicity is mediated by nitroxidative modification of cochlear proteins characterized by nitration of Lmo4","volume":"287","author":"Jamesdaniel","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.neuro.2005.05.010","article-title":"Cisplatin ototoxicity to the rat inner ear: A role for HMG1 and iNOS","volume":"27","author":"Li","year":"2006","journal-title":"Neurotoxicology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1007\/s12035-020-02226-4","article-title":"Lmo4 deficiency enhances susceptibility to cisplatin-induced cochlear apoptosis and hearing loss","volume":"58","author":"Rosati","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.bbrc.2020.10.019","article-title":"Ferrostatin-1 protects auditory hair cells from cisplatin-induced ototoxicity in vitro and in vivo","volume":"533","author":"Hu","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12065","DOI":"10.1111\/jcmm.15839","article-title":"Inhibition of ferroptosis protects House Ear Institute-Organ of Corti 1 cells and cochlear hair cells from cisplatin-induced ototoxicity","volume":"24","author":"Mei","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"174662","DOI":"10.1016\/j.ejphar.2021.174662","article-title":"Cisplatin induces damage of auditory cells: Possible relation with dynamic variation in calcium homeostasis and responding channels","volume":"914","author":"Zhao","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"108513","DOI":"10.1016\/j.heares.2022.108513","article-title":"Cisplatin exposure acutely disrupts mitochondrial bioenergetics in the zebrafish lateral-line organ","volume":"426","author":"Lee","year":"2022","journal-title":"Hear. Res."},{"key":"ref_55","first-page":"72","article-title":"Blood-labyrinth barrier and fluid dynamics of the inner ear","volume":"7","author":"Juhn","year":"2001","journal-title":"Int. Tinnitus J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"eaao0935","DOI":"10.1126\/scitranslmed.aao0935","article-title":"Delivery of therapeutics to the inner ear: The challenge of the blood-labyrinth barrier","volume":"11","author":"Nyberg","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/glia.24095","article-title":"Macrophages in the cochlea; an immunological link between risk factors and progressive hearing loss","volume":"70","author":"Hough","year":"2022","journal-title":"Glia"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Li, Y., Fu, X., Wang, P., Wang, Q., Meng, W., Wang, T., Yang, J., and Chai, R. (2021). The detrimental and beneficial functions of macrophages after cochlear injury. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.631904"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10388","DOI":"10.1073\/pnas.1205210109","article-title":"Perivascular-resident macrophage-like melanocytes in the inner ear are essential for the integrity of the intrastrial fluid\u2013blood barrier","volume":"109","author":"Zhang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00418-016-1436-5","article-title":"Characterisation of cochlear inflammation in mice following acute and chronic noise exposure","volume":"146","author":"Tan","year":"2016","journal-title":"Histochem. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1121\/1.5132545","article-title":"Inflammation associated with noise-induced hearing loss","volume":"146","author":"Frye","year":"2019","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"108518","DOI":"10.1016\/j.heares.2022.108518","article-title":"Inner ear immunity","volume":"419","author":"Keithley","year":"2022","journal-title":"Hear. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"153","DOI":"10.21053\/ceo.2021.00857","article-title":"Inflammatory monocytes infiltrate the spiral ligament and migrate to the basilar membrane after noise exposure","volume":"15","author":"Shin","year":"2022","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.heares.2017.12.009","article-title":"Immune cells and non-immune cells with immune function in mammalian cochleae","volume":"362","author":"Hu","year":"2018","journal-title":"Hear. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1002\/cne.20619","article-title":"Mononuclear phagocytes migrate into the murine cochlea after acoustic trauma","volume":"489","author":"Hirose","year":"2005","journal-title":"J. Comp. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Ramkumar, V., Mukherjea, D., Dhukhwa, A., and Rybak, L.P. (2021). Oxidative stress and inflammation caused by cisplatin ototoxicity. Antioxidants, 10.","DOI":"10.3390\/antiox10121919"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3389\/fncel.2017.00192","article-title":"Resolution of cochlear inflammation: Novel target for preventing or ameliorating drug-, noise-, and age-related hearing loss","volume":"11","author":"Kalinec","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fncel.2017.00106","article-title":"The contribution of immune infiltrates to ototoxicity and cochlear hair cell loss","volume":"11","author":"Wood","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5319\/wjo.v3.i3.89","article-title":"Noise-induced cochlear inflammation","volume":"3","author":"Tan","year":"2013","journal-title":"World J. Otorhinolaryngol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kociszewska, D., and Vlajkovic, S. (2022). Age-related hearing loss: The link between inflammaging, immunosenescence, and gut dysbiosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137348"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"109488","DOI":"10.1016\/j.intimp.2022.109488","article-title":"Spatial architecture of the cochlear immune microenvironment in noise-induced and age-related sensorineural hearing loss","volume":"114","author":"Li","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5057","DOI":"10.1523\/JNEUROSCI.2234-22.2023","article-title":"The stria vascularis in mice and humans is an early site of age-related cochlear degeneration, macrophage dysfunction, and inflammation","volume":"43","author":"Lang","year":"2023","journal-title":"J. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.arr.2017.10.002","article-title":"Chronic inflammation\u2014Inflammaging\u2014In the ageing cochlea: A novel target for future presbycusis therapy","volume":"40","author":"Watson","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.toxlet.2021.10.015","article-title":"The disruption and hyperpermeability of blood-labyrinth barrier mediates cisplatin-induced ototoxicity","volume":"354","author":"Gu","year":"2022","journal-title":"Toxicol. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/j.1600-0773.1995.tb00167.x","article-title":"Mechanism of cisplatin ototoxicity: Antioxidant system","volume":"76","author":"Ravi","year":"1995","journal-title":"Pharmacol. Toxicol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8851525","DOI":"10.1155\/2020\/8851525","article-title":"Cisplatin-induced stria vascularis damage is associated with inflammation and fibrosis","volume":"2020","author":"Zhang","year":"2020","journal-title":"Neural Plast."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0378-5955(00)00182-9","article-title":"Acute changes in cochlear potentials due to cisplatin","volume":"149","author":"Tsukasaki","year":"2000","journal-title":"Hear. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"298ra118","DOI":"10.1126\/scitranslmed.aac5546","article-title":"Endotoxemia-mediated inflammation potentiates aminoglycoside-induced ototoxicity","volume":"7","author":"Koo","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Domingo, I.K., Latif, A., and Bhavsar, A.P. (2022). Pro-inflammatory signalling PRRopels cisplatin-induced toxicity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137227"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev-immunol-030409-101311","article-title":"The sterile inflammatory response","volume":"28","author":"Rock","year":"2010","journal-title":"Annu. Rev. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1007\/s10162-007-0084-9","article-title":"Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF-\u03baB","volume":"8","author":"So","year":"2007","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/s10162-008-0126-y","article-title":"Evidence that cisplatin-induced auditory damage is attenuated by downregulation of pro-inflammatory cytokines via Nrf2\/HO-1","volume":"9","author":"So","year":"2008","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cotox.2017.11.002","article-title":"NF-\u03baB in oxidative stress","volume":"7","author":"Lingappan","year":"2018","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"716469","DOI":"10.3389\/fimmu.2021.716469","article-title":"NF-\u03baB: At the borders of autoimmunity and inflammation","volume":"12","author":"Barnabei","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e51280","DOI":"10.15252\/embr.202051280","article-title":"Toll-like receptor 4 is activated by platinum and contributes to cisplatin-induced ototoxicity","volume":"22","author":"Babolmorad","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1093\/molbev\/msy050","article-title":"Evolutionary origins of Toll-like receptor signaling","volume":"35","author":"Brennan","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1080\/00016480701881811","article-title":"Proapoptotic effects of NF-\u03baB on cisplatin-induced cell death in auditory cell line","volume":"128","author":"Chung","year":"2008","journal-title":"Acta Otolaryngol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"152487","DOI":"10.1016\/j.tox.2020.152487","article-title":"Omeprazole attenuates cisplatin-induced kidney injury through suppression of the TLR4\/NF-\u03baB\/NLRP3 signaling pathway","volume":"440","author":"Gao","year":"2020","journal-title":"Toxicology"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Qu, X., Gao, H., Tao, L., Zhang, Y., Zhai, J., Song, Y., and Zhang, S. (2019). Autophagy inhibition-enhanced assembly of the NLRP3 inflammasome is associated with cisplatin-induced acute injury to the liver and kidneys in rats. J. Biochem. Mol. Toxicol., 33.","DOI":"10.1002\/jbt.22228"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"879021","DOI":"10.3389\/fnagi.2022.879021","article-title":"The NLRP3 inflammasome pathway: A review of mechanisms and inhibitors for the treatment of inflammatory diseases","volume":"14","author":"Blevins","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1038\/s41423-021-00740-6","article-title":"NLRP3 inflammasome activation and cell death","volume":"18","author":"Huang","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"823439","DOI":"10.3389\/fimmu.2022.823439","article-title":"Cochlear marginal cell pyroptosis is induced by cisplatin via NLRP3 inflammasome activation","volume":"13","author":"Yu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4131","DOI":"10.1038\/s41598-019-40425-9","article-title":"Capsaicin protects against cisplatin ototoxicity by changing the STAT3\/STAT1 ratio and activating cannabinoid (CB2) receptors in the cochlea","volume":"9","author":"Bhatta","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1007\/s00204-023-03544-x","article-title":"Apelin-13 protects against cisplatin-induced ototoxicity by inhibiting apoptosis and regulating STAT1 and STAT3","volume":"97","author":"Yin","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e2019","DOI":"10.1038\/cddis.2015.362","article-title":"Loss of STAT1 protects hair cells from ototoxicity through modulation of STAT3, c-Jun, Akt, and autophagy factors","volume":"6","author":"Levano","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1038\/cddis.2011.63","article-title":"Short interfering RNA against STAT1 attenuates cisplatin-induced ototoxicity in the rat by suppressing inflammation","volume":"2","author":"Kaur","year":"2011","journal-title":"Cell Death Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/cr.2011.27","article-title":"Cisplatin ototoxicity involves cytokines and STAT6 signaling network","volume":"21","author":"Kim","year":"2011","journal-title":"Cell Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1125948","DOI":"10.3389\/fimmu.2023.1125948","article-title":"Targeting CXCL1 chemokine signaling for treating cisplatin ototoxicity","volume":"14","author":"Alanisi","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Szczepek, A.J., Dudnik, T., Karayay, B., Sergeeva, V., Olze, H., and Smorodchenko, A. (2020). Mast cells in the auditory periphery of rodents. Brain Sci., 10.","DOI":"10.3390\/brainsci10100697"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Karayay, B., Olze, H., and Szczepek, A.J. (2023). Degranulation of murine resident cochlear mast cells: A possible factor contributing to cisplatin-induced ototoxicity and neurotoxicity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054620"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.1080\/14992027.2018.1455114","article-title":"Protection for medication-induced hearing loss: The state of the science","volume":"57","author":"Hammill","year":"2018","journal-title":"Int. J. Audiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.drudis.2021.11.009","article-title":"The global hearing therapeutic pipeline: 2021","volume":"27","author":"Isherwood","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1055\/s-0041-1735522","article-title":"Investigational medicinal products for the inner ear: Review of clinical trial characteristics in ClinicalTrials.gov","volume":"32","year":"2021","journal-title":"J. Am. Acad. Audiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1097\/MAO.0000000000002194","article-title":"Hearing protection, restoration, and regeneration: An overview of emerging therapeutics for inner ear and central hearing disorders","volume":"40","author":"Schilder","year":"2019","journal-title":"Otol. Neurotol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ejpb.2021.03.008","article-title":"Cisplatin-induced ototoxicity: Updates on molecular mechanisms and otoprotective strategies","volume":"163","author":"Tang","year":"2021","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_106","unstructured":"Freyer, D.R. (2023, October 31). Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy (ClinicalTrials.gov Identifier: NCT00716976), Available online: https:\/\/clinicaltrials.gov\/study\/NCT00716976."},{"key":"ref_107","unstructured":"Ronghe, M.D. (2023, October 31). Cisplatin with or without Sodium Thiosulfate in Treating Young Patients with Stage I, II, or III Childhood Liver Cancer (SIOPEL6) (ClinicalTrial.gov Identifier: NCT00652132), Available online: https:\/\/clinicaltrials.gov\/study\/NCT00652132."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1021\/acs.jmedchem.7b01653","article-title":"Progress in the development of preventative drugs for cisplatin-induced hearing loss","volume":"61","author":"Hazlitt","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1158\/1078-0432.CCR-06-2289","article-title":"Sodium thiosulfate administered six hours after cisplatin does not compromise antineuroblastoma activity","volume":"14","author":"Harned","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1097\/00129492-200411000-00009","article-title":"Prevention of cisplatin ototoxicity using transtympanic N-acetylcysteine and lactate","volume":"25","author":"Choe","year":"2004","journal-title":"Otol. Neurotol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"E87","DOI":"10.1002\/lary.24360","article-title":"Cisplatin otoprotection using transtympanic L-N-acetylcysteine: A pilot randomized study in head and neck cancer patients","volume":"124","author":"Yoo","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/COC.0b013e31822e006d","article-title":"Transtympanic injections of N-acetylcysteine for the prevention of cisplatin-induced ototoxicity: A feasible method with promising efficacy","volume":"36","author":"Riga","year":"2013","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_113","unstructured":"Le, T.N. (2023, October 31). Intratympanic N-Acetylcysteine for Prevention of Cisplatin-Induced Ototoxicity (ClinicalTrials.gov Identifier: NCT04291209), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04291209."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"108646","DOI":"10.1016\/j.heares.2022.108646","article-title":"Manipulating the blood labyrinth barrier with mannitol to prevent cisplatin-induced hearing loss","volume":"426","author":"Noman","year":"2022","journal-title":"Hear. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.heares.2009.03.003","article-title":"Ebselen attenuates cisplatin-induced ROS generation through Nrf2 activation in auditory cells","volume":"251","author":"Kim","year":"2009","journal-title":"Hear. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/00001813-200506000-00013","article-title":"Combined oral delivery of ebselen and allopurinol reduces multiple cisplatin toxicities in rat breast and ovarian cancer models while enhancing anti-tumor activity","volume":"16","author":"Lynch","year":"2005","journal-title":"Anticancer Drugs"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1097\/00005537-199911000-00003","article-title":"Application of antioxidants and other agents to prevent cisplatin ototoxicity","volume":"109","author":"Rybak","year":"1999","journal-title":"Laryngoscope"},{"key":"ref_118","unstructured":"Kil, J. (2023, October 31). SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss (ClinicalTrials.gov Identifier: NCT01451853), Available online: https:\/\/clinicaltrials.gov\/study\/NCT01451853."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.heares.2006.11.012","article-title":"Prevention of noise- and drug-induced hearing loss with D-methionine","volume":"226","author":"Campbell","year":"2007","journal-title":"Hear. Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0378-5955(99)00142-2","article-title":"D-Methionine protects against cisplatin damage to the stria vascularis","volume":"138","author":"Campbell","year":"1999","journal-title":"Hear. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S0378-5955(96)00152-9","article-title":"D-Methionine provides excellent protection from cisplatin ototoxicity in the rat","volume":"102","author":"Campbell","year":"1996","journal-title":"Hear. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1067\/mhn.2002.125299","article-title":"Round window application of D-methionine provides complete cisplatin otoprotection","volume":"126","author":"Korver","year":"2002","journal-title":"Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/00129492-200401000-00007","article-title":"Round window application of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 in cisplatin-induced ototoxicity","volume":"25","author":"Wimmer","year":"2004","journal-title":"Otol. Neurotol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1080\/14992027.2021.1983215","article-title":"Oral D-methionine protects against cisplatin-induced hearing loss in humans: Phase 2 randomized clinical trial in India","volume":"61","author":"Campbell","year":"2022","journal-title":"Int. J. Audiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1097\/MAO.0b013e31818599d5","article-title":"Cisplatin-induced ototoxicity: Effect of intratympanic dexamethasone injections","volume":"29","author":"Hill","year":"2008","journal-title":"Otol. Neurotol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1177\/0194599811406673","article-title":"Intratympanic dexamethasone to prevent cisplatin ototoxicity: A guinea pig model","volume":"145","author":"Murphy","year":"2011","journal-title":"Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.otohns.2007.05.068","article-title":"The protective effect of intratympanic dexamethasone on cisplatin-induced ototoxicity in guinea pigs","volume":"137","author":"Daldal","year":"2007","journal-title":"Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.2147\/IJN.S195336","article-title":"Dexamethasone-loaded injectable silk-polyethylene glycol hydrogel alleviates cisplatin-induced ototoxicity","volume":"14","author":"Chen","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1159\/000441833","article-title":"The sustained-exposure dexamethasone formulation OTO-104 offers effective protection against cisplatin-induced hearing loss","volume":"21","author":"Fernandez","year":"2016","journal-title":"Audiol. Neurotol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.actbio.2017.02.019","article-title":"Polymeric nanoparticles loaded with dexamethasone or \u03b1-tocopheryl succinate to prevent cisplatin-induced ototoxicity","volume":"53","author":"Aguilar","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_131","first-page":"3567","article-title":"A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration","volume":"10","author":"Sun","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ijporl.2019.04.003","article-title":"Dexamethasone-loaded chitosan-based genipin-cross-linked hydrogel for prevention of cisplatin induced ototoxicity in Guinea pig model","volume":"122","author":"Durankaya","year":"2019","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1007\/s00405-019-05635-x","article-title":"Comparison of the protective efficacy between intratympanic dexamethasone and resveratrol treatments against cisplatin-induced ototoxicity: An experimental study","volume":"276","author":"Simsek","year":"2019","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1177\/0194599814524894","article-title":"Prevention of cisplatin-induced hearing loss by intratympanic dexamethasone: A randomized controlled study","volume":"150","author":"Marshak","year":"2014","journal-title":"Otolaryngol.\u2014Head Neck Surg."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1097\/AUD.0000000000001119","article-title":"Evaluating the efficacy of intratympanic dexamethasone in protecting against irreversible hearing loss in patients on cisplatin-based cancer treatment: A randomized controlled Phase IIIB clinical trial","volume":"43","author":"Moreno","year":"2022","journal-title":"Ear Hear."},{"key":"ref_136","unstructured":"Bishop, K. (2023, November 01). Study of OTO-104 in Subjects at Risk from Cisplatin-Induced Hearing Loss (ClinicalTrials.gov Identifier: NCT02997189), Available online: https:\/\/clinicaltrials.gov\/study\/NCT02997189."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1523\/JNEUROSCI.3111-15.2016","article-title":"Adenosine A1 receptor protects against cisplatin ototoxicity by suppressing the NOX3\/STAT1 inflammatory pathway in the cochlea","volume":"36","author":"Kaur","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Jiang, Y., Li, Z., Ma, Q., Dong, W., Yao, Q., and Yu, D. (2023). Aucubin protects mouse cochlear hair cells from cisplatin-induced ototoxicity via activation of the PI3K\/AKT\/STAT3 pathway. Biochem. Pharmacol., 209.","DOI":"10.1016\/j.bcp.2023.115440"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Ramkumar, V., and Rybak, L.P. (2018). Inflammatory Mechanisms in Mediating Hearing Loss, Springer International Publishing.","DOI":"10.1007\/978-3-319-92507-3"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Gunewardene, N., Guo, C.X., Wong, A.C., Thorne, P., and Vlajkovic, S. (2013). Adenosine amine congener ameliorates cisplatin-induced hearing loss. World J. Otorhinolaryngol., 3.","DOI":"10.5319\/wjo.v3.i3.100"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1089\/ars.2021.0183","article-title":"Cisplatin chemotherapy and cochlear damage: Otoprotective and chemosensitization properties of polyphenols","volume":"36","author":"Fetoni","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/s41598-020-57965-0","article-title":"The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity","volume":"10","author":"Paciello","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Umugire, A., Nam, Y.S., Nam, Y.E., Choi, Y.M., Choi, S.M., Lee, S., Cho, J.H., and Cho, H.-H. (2023). Protective effect of avenanthramide-C on auditory hair cells against oxidative stress, inflammatory cytokines, and DNA damage in cisplatin-induced ototoxicity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032947"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"6884","DOI":"10.1038\/s41598-019-43412-2","article-title":"Avenanthramide C from germinated oats exhibits anti-allergic inflammatory effects in mast cells","volume":"9","author":"Dhakal","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.freeradbiomed.2007.10.036","article-title":"Avenanthramides, polyphenols from oats, inhibit IL-1\u03b2-induced NF-\u03baB activation in endothelial cells","volume":"44","author":"Guo","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"107905","DOI":"10.1016\/j.heares.2020.107905","article-title":"Lovastatin protects against cisplatin-induced hearing loss in mice","volume":"389","author":"Fernandez","year":"2020","journal-title":"Hear. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16545\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:26:28Z","timestamp":1760131588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,20]]},"references-count":146,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242216545"],"URL":"https:\/\/doi.org\/10.3390\/ijms242216545","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,20]]}}}