{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:38:29Z","timestamp":1792291109815,"version":"4.4.0"},"reference-count":117,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Cisplatin is a highly effective broad-spectrum anticancer drug, but its severe ototoxicity limits its clinical application. Cisplatin ototoxicity is mainly manifested as irreversible hearing loss, and its mechanism involves various pathways such as DNA damage, oxidative stress, inflammatory response, mitochondrial dysfunction, and ferroptosis. In recent years, natural polyphenols have shown great potential in combating cisplatin ototoxicity due to their powerful antioxidant, anti-inflammatory and anti-apoptotic properties.A variety of polyphenolic compounds, such as resveratrol, curcumin, quercetin, etc., can effectively attenuate the damage of cisplatin on Corti organs, spiral ganglion neurons and vascular striatum by scavenging free radicals, inhibiting the release of inflammatory factors, and regulating the expression of apoptosis-related proteins. In addition, some polyphenols can enhance the anti-tumour effect while antagonizing ototoxicity.Although polyphenols show good application prospects in the prevention and treatment of cisplatin ototoxicity, there are still some problems that need to be solved, such as the low bioavailability of polyphenols, the mechanism of action has not yet been fully elucidated, the optimal dosing regimen has not yet been determined, whether there is any superimposed effect of combining the various types of polyphenols, and whether the oral polyphenols can exert an otoprotective effect through the regulation of the intestinal flora through the intestinal-auricular axis.This study provides new insights into polyphenols as potential drug candidates for CIO by summarising the cytotoxic mechanisms of cisplatin and the mechanism of action of polyphenols targeting these mechanisms in order to retard the progression of CIO. It provides new ideas and approaches for the next step focusing on the development of highly effective and low-toxic polyphenols for clinical control of cisplatin ototoxicity.<\/jats:p>","DOI":"10.3389\/fphar.2025.1586243","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T05:22:51Z","timestamp":1745558571000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Studies on the mechanism of ototoxic action of cisplatin and the antagonistic effect of polyphenolic compounds"],"prefix":"10.3389","volume":"16","author":[{"given":"Shengyu","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenpeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoming","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/ptr.7305","article-title":"Curcumin and its derivatives in cancer therapy: potentiating antitumor activity of cisplatin and reducing side effects","volume":"36","author":"Abadi","year":"2022","journal-title":"Phytotherapy Res. PTR"},{"key":"B2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.3390\/biom10020221","article-title":"Therapeutic potential of plant phenolic acids in the treatment of cancer","volume":"10","author":"Abotaleb","year":"2020","journal-title":"Biomolecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s12937-016-0217-2","article-title":"An overview on the role of dietary phenolics for the treatment of cancers","volume":"15","author":"Anantharaju","year":"2016","journal-title":"Nutr. J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"15790","DOI":"10.3390\/ijms232415790","article-title":"Pericytes of stria Vascularis are targets of cisplatin-induced ototoxicity: new insights into the molecular mechanisms involved in blood-labyrinth barrier breakdown","volume":"23","author":"Anfuso","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"189","DOI":"10.22038\/IJORL.2023.71786.3452","article-title":"Curcumin prevents ototoxicity induced by cisplatin as evaluated with OAE","volume":"35","author":"Arwanda","year":"2023","journal-title":"Iran. J. otorhinolaryngology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e51280","DOI":"10.15252\/embr.202051-280","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":"B7","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1016\/j.ijporl.2012.06.003","article-title":"Prevention of cisplatin ototoxicity: efficacy of micronized flavonoid fraction in a Guinea pig model","volume":"76","author":"Ba\u015fo\u011flu","year":"2012","journal-title":"Int. J. Pediatr. otorhinolaryngology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.15252\/emmm.201606230","article-title":"Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy","volume":"9","author":"Benkafadar","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","first-page":"e2921","DOI":"10.1038\/cddis.2017.314","article-title":"Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection against cisplatin-based ototoxicity","volume":"8","author":"Borse","year":"2017","journal-title":"Cell death and Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"4573","DOI":"10.3390\/cancers14194573","article-title":"Advances in dietary phenolic compounds to improve chemosensitivity of anticancer drugs","volume":"14","author":"Bouyahya","year":"2022","journal-title":"Cancers"},{"key":"B12","doi-asserted-by":"publisher","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":"B13","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1124\/pharmrev.124.001195","article-title":"Pharmacological approaches to hearing loss","volume":"76","author":"Cederroth","year":"2024","journal-title":"Pharmacol. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"8000","DOI":"10.1039\/d1nr07921b","article-title":"Epigallocatechin gallate-loaded tetrahedral DNA nanostructures as a novel inner ear drug delivery system","volume":"14","author":"Chen","year":"2022","journal-title":"Nanoscale"},{"key":"B15","doi-asserted-by":"publisher","first-page":"223S","DOI":"10.1093\/ajcn\/81.1.223S","article-title":"Polyphenols in foods are more complex than often thought","volume":"81","author":"Cheynier","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"B16","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.ijporl.2013.12.024","article-title":"Protective effect of silymarin against cisplatin-induced ototoxicity","volume":"78","author":"Cho","year":"","journal-title":"Int. J. Pediatr. otorhinolaryngology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1017\/S0022215114000553","article-title":"Protective effect of (-)-epigallocatechin-3-gallate against cisplatin-induced ototoxicity","volume":"128","author":"Cho","year":"","journal-title":"J. laryngology otology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/s1734-1140(11)70582-5","article-title":"Anti-apoptotic effect of phloretin on cisplatin-induced apoptosis in HEI-OC1 auditory cells","volume":"63","author":"Choi","year":"2011","journal-title":"Pharmacol. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1016\/j.ijporl.2014.10.013","article-title":"Effects of caffeic acid on cisplatin-induced hair cell damage in HEI-OC1 auditory cells","volume":"78","author":"Choi","year":"2014","journal-title":"Int. J. Pediatr. otorhinolaryngology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"458","DOI":"10.3390\/pr8040458","article-title":"Resveratrol nanoparticles: a promising therapeutic advancement over native resveratrol","volume":"8","author":"Chung","year":"2020","journal-title":"Processes"},{"key":"B21","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1634\/theoncologist.2016-0319","article-title":"A systematic review of strategies to prevent cisplatin-induced nephrotoxicity","volume":"22","author":"Crona","year":"2017","journal-title":"Oncol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.3390\/antiox13121552","article-title":"Polyphenol-derived microbiota metabolites and cardiovascular health: a concise review of human studies","volume":"13","author":"Da C Pinaffi-Langley","year":"2024","journal-title":"Antioxidants Basel, Switz."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1430469","DOI":"10.3389\/fphar.2024.1430469","article-title":"Apoptosis, autophagy, ferroptosis, and pyroptosis in cisplatin-induced ototoxicity and protective agents","volume":"15","author":"Dai","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e450","DOI":"10.1016\/S2542-5196(19)30212-8","article-title":"Associations between habitual flavonoid intake and hospital admissions for atherosclerotic cardiovascular disease: a prospective cohort study","volume":"3","author":"Dalgaard","year":"2019","journal-title":"Lancet. Planet. health"},{"key":"B25","doi-asserted-by":"publisher","first-page":"12","DOI":"10.5935\/0946-5448.20150003","article-title":"The chemopreventive effect of Ginkgo biloba extract 761 against cisplatin ototoxicity: a pilot study","volume":"19","author":"Dias","year":"2015","journal-title":"Int. tinnitus J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"141","DOI":"10.5152\/tao.2016.1974","article-title":"Effect of ecklonia Cava polyphenol extract in house ear institute-organ of Corti 1 cells against cisplatin ototoxicity: a preliminary study","volume":"54","author":"D\u00fczenli","year":"2016","journal-title":"Turkish archives otorhinolaryngology"},{"key":"B27","doi-asserted-by":"publisher","first-page":"106939","DOI":"10.1016\/j.ejps.2024.106939","article-title":"Advances in understanding cisplatin-induced toxicity: molecular mechanisms and protective strategies","volume":"203","author":"Elmorsy","year":"2024","journal-title":"Eur. Fed. Pharm. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2777","DOI":"10.1080\/13880209.2016.1177093","article-title":"Protective effect of Pycnogenol on cisplatin-induced ototoxicity in rats","volume":"54","author":"Eryilmaz","year":"2016","journal-title":"Pharm. Biol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e169","DOI":"10.1097\/MAO.0000000000000302","article-title":"Curcuma longa (curcumin) decreases in vivo cisplatin-induced ototoxicity through heme oxygenase-1 induction","volume":"35","author":"Fetoni","year":"2014","journal-title":"Otology and Neurotol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1038\/bjc.2015.359","article-title":"Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling","volume":"113","author":"Fetoni","year":"2015","journal-title":"Br. J. cancer"},{"key":"B31","doi-asserted-by":"publisher","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":"2022","journal-title":"Antioxidants and redox Signal."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4272","DOI":"10.3390\/ijms25084272","article-title":"Unveiling the role of oxidative stress in cochlear hair cell death: prospective phytochemical therapeutics against sensorineural hearing loss","volume":"25","author":"Gill","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/s41577-019-0215-7","article-title":"DAMP-sensing receptors in sterile inflammation and inflammatory diseases","volume":"20","author":"Gong","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3454","DOI":"10.3390\/nu15153454","article-title":"Polyphenols and their impact on the prevention of neurodegenerative diseases and development","volume":"15","author":"Grabska-Koby\u0142ecka","year":"2023","journal-title":"Nutrients"},{"key":"B35","doi-asserted-by":"publisher","first-page":"229","DOI":"10.5152\/iao.2019.5902","article-title":"Assessment of the effectiveness of quercetin on cisplatin-induced ototoxicity in rats","volume":"15","author":"G\u00fcndo\u011fdu","year":"2019","journal-title":"J. Int. Adv. otology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"nwae100","DOI":"10.1093\/nsr\/nwae100","article-title":"Superparamagnetic iron oxide nanoparticle regulates microbiota-gut-inner ear axis for hearing protection","volume":"11","author":"Guo","year":"2024","journal-title":"Natl. Sci. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.tips.2004.03.005","article-title":"Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling","volume":"25","author":"Hong","year":"2004","journal-title":"Trends Pharmacol. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"19329","DOI":"10.1038\/srep19329","article-title":"NRF2 is a key target for prevention of noise-induced hearing loss by reducing oxidative damage of cochlea","volume":"6","author":"Honkura","year":"2016","journal-title":"Sci. Rep."},{"key":"B39","doi-asserted-by":"publisher","first-page":"110939","DOI":"10.1016\/j.cbi.2024.110939","article-title":"Quercetin attenuates cisplatin-induced mitochondrial apoptosis via PI3K\/Akt mediated inhibition of oxidative stress in pericytes and improves the blood labyrinth barrier permeability","volume":"393","author":"Huang","year":"2024","journal-title":"Chemico-biological Interact."},{"key":"B40","doi-asserted-by":"publisher","first-page":"3746","DOI":"10.3390\/molecules28093746","article-title":"Combination chemotherapy with selected polyphenols in preclinical and clinical studies-an update overview","volume":"28","author":"Jakobu\u0161i\u0107 Brala","year":"2023","journal-title":"Mol. Basel, Switz."},{"key":"B41","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.ijporl.2019.02.001","article-title":"The protective role of ferulic acid against cisplatin-induced ototoxicity","volume":"120","author":"Jo","year":"2019","journal-title":"Int. J. Pediatr. otorhinolaryngology"},{"key":"B42","doi-asserted-by":"publisher","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":"B43","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.ijporl.2016.03.019","article-title":"Evaluation of the protective effects of hesperetin against cisplatin-induced ototoxicity in a rat animal model","volume":"85","author":"Kara","year":"2016","journal-title":"Int. J. Pediatr. otorhinolaryngology"},{"key":"B44","doi-asserted-by":"publisher","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 and Dis."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1007\/s10495-008-0242-5","article-title":"Epicatechin protects auditory cells against cisplatin-induced death","volume":"13","author":"Kim","year":"2008","journal-title":"Apoptosis Int. J. Program. cell death"},{"key":"B46","doi-asserted-by":"publisher","first-page":"e43967","DOI":"10.1371\/journal.pone.0043967","article-title":"(-)-Epigallocatechin-3-gallate protects against NO-induced ototoxicity through the regulation of caspase- 1, caspase-3, and NF-\u03baB activation","volume":"7","author":"Kim","year":"2012","journal-title":"PloS one"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.3390\/ijms18122589","article-title":"The role of resveratrol in cancer therapy","volume":"18","author":"Ko","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"115099","DOI":"10.1016\/j.fct.2024.115099","article-title":"Apigenin attenuates cisplatin-induced hair cell damage in the zebrafish lateral line","volume":"194","author":"Kong","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/s41419-019-1386-7","article-title":"Pasireotide protects mammalian cochlear hair cells from gentamicin ototoxicity by activating the PI3K-Akt pathway","volume":"10","author":"Kucharava","year":"2019","journal-title":"Cell death and Dis."},{"key":"B50","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.clnu.2013.03.008","article-title":"Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy","volume":"32","author":"Lecumberri","year":"2013","journal-title":"Clin. Nutr. Edinb. Scotl."},{"key":"B51","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3390\/ijms22010113","article-title":"Dose-dependent effects of resveratrol on cisplatin-induced hearing loss","volume":"22","author":"Lee","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.toxlet.2010.09.013","article-title":"Epicatechin protects the auditory organ by attenuating cisplatin-induced ototoxicity through inhibition of ERK","volume":"199","author":"Lee","year":"2010","journal-title":"Toxicol. Lett."},{"key":"B53","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ijporl.2014.11.008","article-title":"Protective effect of resveratrol against cisplatin-induced ototoxicity in HEI-OC1 auditory cells","volume":"79","author":"Lee","year":"","journal-title":"Int. J. Pediatr. otorhinolaryngology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1177\/0960327114567766","article-title":"Protective role of quercetin against cisplatin-induced hair cell damage in zebrafish embryos","volume":"34","author":"Lee","year":"","journal-title":"Hum. and Exp. Toxicol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1021\/acs.chemrestox.6b00413","article-title":"Dietary phytochemicals and cancer chemoprevention: a perspective on oxidative stress, inflammation, and epigenetics","volume":"29","author":"Li","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"105852","DOI":"10.1016\/j.tiv.2024.105852","article-title":"Schisandrin B protect inner hair cells from cisplatin by inhibiting celluar oxidative stress and apoptosis","volume":"99","author":"Li","year":"2024","journal-title":"Toxicol. vitro Int. J. Publ. Assoc. BIBRA"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e23750","DOI":"10.1016\/j.heliyon.2023.e23750","article-title":"Formononetin ameliorates cisplatin-induced hair cell death via activation of the PI3K\/AKT-Nrf2 signaling pathway","volume":"10","author":"Li","year":"","journal-title":"Heliyon"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1197051","DOI":"10.3389\/fncel.2023.1197051","article-title":"Cisplatin ototoxicity mechanism and antagonistic intervention strategy: a scope review","volume":"17","author":"Li","year":"","journal-title":"Front. Cell. Neurosci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.freeradbiomed.2023.11.025","article-title":"Drug screening identifies aldose reductase as a novel target for treating cisplatin-induced hearing loss","volume":"210","author":"Liao","year":"2024","journal-title":"Free Radic. Biol. and Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"115962","DOI":"10.1016\/j.bcp.2023.115962","article-title":"Puerarin inhibits cisplatin-induced ototoxicity in mice through regulation of TRPV1-dependent calcium overload","volume":"220","author":"Lin","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"3305","DOI":"10.3390\/nu16193305","article-title":"Dietary polyphenols as anti-aging agents: targeting the hallmarks of aging","volume":"16","author":"Liu","year":"2024","journal-title":"Nutrients"},{"key":"B62","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1139\/bcb-2020-0459","article-title":"Resveratrol upregulates miR-455-5p to antagonize cisplatin ototoxicity via modulating the PTEN-PI3K-AKT axis","volume":"99","author":"Liu","year":"2021","journal-title":"Biochem. cell Biol. = Biochimie Biol. Cell."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2341470","DOI":"10.1080\/13510002.2024.2341470","article-title":"Hesperidin activates Nrf2 to protect cochlear hair cells from cisplatin-induced damage","volume":"29","author":"Lou","year":"2024","journal-title":"Redox Rep. Commun. free Radic. Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1090034","DOI":"10.1155\/2022\/1090034","article-title":"Novel application of eupatilin for effectively attenuating cisplatin-induced auditory hair cell death via mitochondrial apoptosis pathway","volume":"2022","author":"Lu","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B65","doi-asserted-by":"publisher","first-page":"117174","DOI":"10.1016\/j.biopha.2024.117174","article-title":"Mangiferin alleviates cisplatin-induced ototoxicity in sensorineural hearing loss","volume":"178","author":"Lu","year":"2024","journal-title":"Biomed. and Pharmacother. = Biomedecine and Pharmacother."},{"key":"B66","doi-asserted-by":"publisher","first-page":"2468853","DOI":"10.1080\/14756366.2025.2468853","article-title":"Ferroptosis and hearing loss: from molecular mechanisms to therapeutic interventions","volume":"40","author":"Lv","year":"2025","journal-title":"J. enzyme inhibition Med. Chem."},{"key":"B67","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.3390\/nu14081574","article-title":"The employment of genera Vaccinium, citrus, olea, and CynaraPolyphenols for the reduction of selected anti-cancer drug side effects","volume":"14","author":"Maiuolo","year":"2022","journal-title":"Nutrients"},{"key":"B69","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.fct.2013.12.024","article-title":"Ferulic acid: pharmacological and toxicological aspects","volume":"65","author":"Mancuso","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1089\/ars.2010.3497","article-title":"NOX3 NADPH oxidase couples transient receptor potential vanilloid 1 to signal transducer and activator of transcription 1-mediated inflammation and hearing loss","volume":"14","author":"Mukherjea","year":"2011","journal-title":"Antioxidants and redox Signal."},{"key":"B71","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.3390\/medicina59112045","article-title":"Polyphenols in inner ear neurobiology, health and disease: from bench to clinics","volume":"59","author":"Osakabe","year":"2023","journal-title":"Med. Kaunas. Lith."},{"key":"B72","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.bjorl.2017.10.009","article-title":"The protective effects of whortleberry extract against cisplatin-induced ototoxicity in rats","volume":"85","author":"\u00d6zdemir","year":"2019","journal-title":"Braz. J. otorhinolaryngology"},{"key":"B73","doi-asserted-by":"publisher","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":"B75","doi-asserted-by":"publisher","first-page":"370","DOI":"10.5530\/pj.2023.15.57","article-title":"The effect of combination between green tea extract and curcumin extract from Mt. Lawu on BAX, bcl-2 and caspase-3 in cisplatin-induced rat models","volume":"15","author":"Primadewi","year":"2023","journal-title":"Pharmacogn. J."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.3390\/antiox10121919","article-title":"Oxidative stress and inflammation caused by cisplatin ototoxicity","volume":"10","author":"Ramkumar","year":"2021","journal-title":"Antioxidants Basel, Switz."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.3390\/antiox13121578","article-title":"Cisplatin-induced hearing loss, oxidative stress, and antioxidants as a therapeutic strategy-A state-of-the-art review","volume":"13","author":"Rose","year":"2024","journal-title":"Antioxidants Basel, Switz."},{"key":"B78","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1055\/s-0039-1684048","article-title":"Mechanisms of cisplatin-induced ototoxicity and prevention","volume":"40","author":"Rybak","year":"2019","journal-title":"Seminars Hear."},{"key":"B79","doi-asserted-by":"publisher","first-page":"153218","DOI":"10.1016\/j.phymed.2020.153218","article-title":"Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: a comparative, randomized, double-blind, placebo-controlled clinical trial","volume":"70","author":"Saghatelyan","year":"2020","journal-title":"Phytomedicine Int. J. phytotherapy Phytopharm."},{"key":"B80","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3390\/life15010078","article-title":"Is Punica granatum efficient against sepsis? A comparative study of amifostine versus pomegranate","volume":"15","author":"Sahin","year":"2025","journal-title":"Life Basel, Switz."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1097\/MAO.0000000000000403","article-title":"Attenuation of cisplatin ototoxicity by otoprotective effects of nanoencapsulated curcumin and dexamethasone in a Guinea pig model","volume":"35","author":"Salehi","year":"2014","journal-title":"Otological Soc. Am. Neurotol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"603235","DOI":"10.3389\/fphar.2020.603235","article-title":"Curcumin nanoparticle enhances the anticancer effect of cisplatin by inhibiting PI3K\/AKT and JAK\/STAT3 pathway in rat ovarian carcinoma induced by DMBA","volume":"11","author":"Sandhiutami","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1016\/j.ijbiomac.2019.06.180","article-title":"Cytochrome c: an extreme multifunctional protein with a key role in cell fate","volume":"136","author":"Santucci","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"812","DOI":"10.3390\/antiox12040812","article-title":"Impact of gut microbiota in brain ageing: polyphenols as beneficial modulators","volume":"12","author":"Sarubbo","year":"2023","journal-title":"Antioxidants Basel, Switz."},{"key":"B85","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.3390\/nu12092499","article-title":"Interaction between gut microbiota and curcumin: a new key of understanding for the health effects of curcumin","volume":"12","author":"Scazzocchio","year":"2020","journal-title":"Nutrients"},{"key":"B86","doi-asserted-by":"publisher","first-page":"3843","DOI":"10.1523\/JNEUROSCI.5842-08.2009","article-title":"Cisplatin-induced hair cell death requires STAT1 and is attenuated by epigallocatechin gallate","volume":"29","author":"Schmitt","year":"2009","journal-title":"J. Neurosci. official J. Soc. Neurosci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"114587","DOI":"10.1016\/j.jep.2021.114587","article-title":"Efficacy and safety of standardized Ginkgo biloba L. leaves extract as an adjuvant therapy for sudden sensorineural hearing loss: a systematic review and meta-analysis","volume":"282","author":"Si","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"B88","doi-asserted-by":"publisher","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. Fed. Oto-Rhino-Laryngological"},{"key":"B89","doi-asserted-by":"publisher","first-page":"7889","DOI":"10.1038\/s41598-024-55614-4","article-title":"Nobiletin alleviates cisplatin-induced ototoxicity via activating autophagy and inhibiting NRF2\/GPX4-mediated ferroptosis","volume":"14","author":"Song","year":"2024","journal-title":"Sci. Rep."},{"key":"B90","doi-asserted-by":"publisher","first-page":"7753","DOI":"10.3390\/ijms21207753","article-title":"Antioxidant supplementation in the treatment of neurotoxicity induced by platinum-based chemotherapeutics\u2014a review","volume":"21","author":"Stankovic","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.tcb.2020.02.009","article-title":"Emerging mechanisms and disease relevance of ferroptosis","volume":"30","author":"Stockwell","year":"2020","journal-title":"Trends cell Biol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"eadk9878","DOI":"10.1126\/sciadv.adk9878","article-title":"Macrophage depletion protects against cisplatin-induced ototoxicity and nephrotoxicity","volume":"10","author":"Sung","year":"2024","journal-title":"Sci. Adv."},{"key":"B93","doi-asserted-by":"publisher","first-page":"207","DOI":"10.22038\/IJORL.2023.69813.3368","article-title":"The use of herbal medicine in sudden sensorineural hearing loss in diabetic patients","volume":"35","author":"Tajdini","year":"2023","journal-title":"Iran. J. otorhinolaryngology"},{"key":"B94","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.bjorl.2021.07.001","article-title":"The effect of genistein on cisplatin induced ototoxicity and oxidative stress","volume":"88","author":"Tan","year":"2022","journal-title":"Braz. J. otorhinolaryngology"},{"key":"B95","doi-asserted-by":"publisher","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":"B96","doi-asserted-by":"publisher","first-page":"16545","DOI":"10.3390\/ijms242216545","article-title":"Molecular characteristics of cisplatin-induced ototoxicity and therapeutic interventions","volume":"24","author":"Tan","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B97","first-page":"4416","article-title":"Systemic application of honokiol prevents cisplatin ototoxicity without compromising its antitumor effect","volume":"10","author":"Tan","year":"2020","journal-title":"Am. J. cancer Res."},{"key":"B98","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: molecular mechanisms and health implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res."},{"key":"B99","doi-asserted-by":"publisher","first-page":"e14403","DOI":"10.1111\/cns.14403","article-title":"Cinchonine and cinchonidine alleviate cisplatin-induced ototoxicity by regulating PI3K-AKT signaling","volume":"30","author":"Tang","year":"2024","journal-title":"CNS Neurosci. and Ther."},{"key":"B100","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1186\/s12951-024-02686-z","article-title":"Crosslinked-hybrid nanoparticle embedded in thermogel for sustained co-delivery to inner ear","volume":"22","author":"Thakur","year":"2024","journal-title":"J. nanobiotechnology"},{"key":"B101","doi-asserted-by":"publisher","first-page":"118869","DOI":"10.1016\/j.lfs.2020.118869","article-title":"Phloretin and phloridzin guard against cisplatin-induced nephrotoxicity in mice through inhibiting oxidative stress and inflammation","volume":"266","author":"Un","year":"2021","journal-title":"Life Sci."},{"key":"B102","doi-asserted-by":"publisher","first-page":"10244","DOI":"10.3390\/ijms231810244","article-title":"Combination therapy using polyphenols: an efficient way to improve antitumoral activity and reduce resistance","volume":"23","author":"Vladu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B103","doi-asserted-by":"publisher","first-page":"115197","DOI":"10.1016\/j.ejmech.2023.115197","article-title":"EGCG adjuvant chemotherapy: current status and future perspectives","volume":"250","author":"Wang","year":"","journal-title":"Eur. J. Med. Chem."},{"key":"B104","doi-asserted-by":"publisher","first-page":"2210733","DOI":"10.1155\/2022\/2210733","article-title":"Nrf2 knockout affected the ferroptosis signaling pathway against cisplatin-induced hair cell-like HEI-OC1 cell death","volume":"2022","author":"Wang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B105","doi-asserted-by":"publisher","first-page":"114045","DOI":"10.1016\/j.biopha.2022.114045","article-title":"Cisplatin-induced ototoxicity: from signaling network to therapeutic targets","volume":"157","author":"Wang","year":"","journal-title":"Biomed. and Pharmacother. = Biomedecine and Pharmacother."},{"key":"B106","doi-asserted-by":"publisher","first-page":"112464","DOI":"10.1016\/j.intimp.2024.112464","article-title":"Resveratrol shields against cisplatin-induced ototoxicity through epigenetic lncRNA GAS5 modulation of miR-455-5p\/PTEN pathway","volume":"138","author":"Wu","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"B107","doi-asserted-by":"publisher","first-page":"100955","DOI":"10.1016\/j.lanwpc.2023.100955","article-title":"Tea consumption and attenuation of biological aging: a longitudinal analysis from two cohort studies","volume":"42","author":"Xiang","year":"2023","journal-title":"Lancet regional health. West. Pac."},{"key":"B108","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1080\/00016480410018278","article-title":"(-)-Epigallocatechin-3-gallate protects cultured spiral ganglion cells from H2O2-induced oxidizing damage","volume":"124","author":"Xie","year":"2004","journal-title":"Acta oto-laryngologica"},{"key":"B109","doi-asserted-by":"publisher","first-page":"119208","DOI":"10.1016\/j.bbamcr.2021.119208","article-title":"Puerarin attenuates cisplatin-induced apoptosis of hair cells through the mitochondrial apoptotic pathway","volume":"1869","author":"Xu","year":"2022","journal-title":"Biochimica biophysica acta. Mol. cell Res."},{"key":"B110","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s00405-011-1582-2","article-title":"Reduction of cisplatin ototoxicity in rats by oral administration of pomegranate extract","volume":"269","author":"Yazici","year":"2012","journal-title":"Eur. Fed. Oto-Rhino-Laryngological"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1230125","DOI":"10.3389\/fmicb.2023.1230125","article-title":"Association between gut microbiota and sensorineural hearing loss: a Mendelian randomization study","volume":"14","author":"Yin","year":"2023","journal-title":"Front. Microbiol."},{"key":"B112","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1002\/ptr.3027","article-title":"Pueraria thunbergiana inhibits cisplatin-induced damage of HEI-OC1 auditory cells through scavenging free radicals","volume":"24","author":"Yu","year":"2010","journal-title":"Phytotherapy Res. PTR"},{"key":"B113","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1080\/13880209.2023.2190782","article-title":"Efficacy and safety of Ginkgo biloba extract as an adjuvant in the treatment of Chinese patients with sudden hearing loss: a meta-analysis","volume":"61","author":"Yuan","year":"2023","journal-title":"Pharm. Biol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.ijporl.2011.12.021","article-title":"Protective role of resveratrol against cisplatin induced ototoxicity in Guinea pigs","volume":"76","author":"Yumusakhuylu","year":"2012","journal-title":"Int. J. Pediatr. otorhinolaryngology"},{"key":"B115","doi-asserted-by":"publisher","first-page":"52","DOI":"10.4236\/ym.2025.91006","article-title":"Flavonoids as modulators of Nrf2 signaling pathway in alleviating cisplatin-induced organ toxicity","volume":"9","author":"Zhang","year":"2025","journal-title":"Yangtze Med."},{"key":"B116","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.ejps.2016.03.017","article-title":"Effects of epigallocatechin-3-gallate on proliferation and differentiation of mouse cochlear neural stem cells: involvement of PI3K\/Akt signaling pathway","volume":"88","author":"Zhang","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"B117","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.neuro.2022.03.005","article-title":"The protective effect of rutin against the cisplatin-induced cochlear damage in vitro","volume":"90","author":"Zheng","year":"2022","journal-title":"Neurotoxicology"},{"key":"B118","doi-asserted-by":"publisher","first-page":"515","DOI":"10.3390\/nu8080515","article-title":"Natural polyphenols for prevention and treatment of cancer","volume":"8","author":"Zhou","year":"2016","journal-title":"Nutrients"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1586243\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T05:22:53Z","timestamp":1745558573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1586243\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,25]]},"references-count":117,"alternative-id":["10.3389\/fphar.2025.1586243"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1586243","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,25]]},"article-number":"1586243"}}