{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:04:31Z","timestamp":1792091071923,"version":"4.4.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T00:00:00Z","timestamp":1555372800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007051","name":"Uppsala University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["HNO"],"published-print":{"date-parts":[[2019,6]]},"DOI":"10.1007\/s00106-019-0663-1","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T13:03:35Z","timestamp":1555419815000},"page":"434-439","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Pharmacological intervention in the field of ototoxicity","Pharmakologische Intervention im Bereich der Ototoxizit\u00e4t"],"prefix":"10.1007","volume":"67","author":[{"given":"G.","family":"Laurell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,16]]},"reference":[{"key":"663_CR1","doi-asserted-by":"publisher","first-page":"248254","DOI":"10.1016\/j.jcf.2014.07.009","volume":"14","author":"G Al-Malky","year":"2015","unstructured":"Al-Malky G, Dawson SJ, Sirimanna T, Bagkeris E, Suri R (2015) High-frequency audiometry reveals high prevalence of aminoglycoside ototoxicity in children with cystic fibrosis. J\u00a0Cyst Fibros 14:248254","journal-title":"J Cyst Fibros"},{"key":"663_CR2","first-page":"CD009219","volume":"9","author":"JW As van","year":"2016","unstructured":"van As JW, van den Berg H, van Dalen EC (2016) Medical interventions for the prevention of platinum-induced hearing loss in children with cancer. Cochrane Database Syst Rev 9:CD9219","journal-title":"Cachrane Database Syst Rev"},{"key":"663_CR3","first-page":"CD010885","volume":"7","author":"JW As van","year":"2018","unstructured":"van As JW, van den Berg H, van Dalen EC (2018) Different infusion durations for preventing platinum-induced hearing loss in children with cancer. Cochrane Database Syst Rev 7:CD10885","journal-title":"Cochrane Database Syst Rev"},{"key":"663_CR4","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1111\/j.1365-2796.1993.tb00691.x","volume":"233","author":"U Axdorph","year":"1993","unstructured":"Axdorph U, Bj\u00f6rkholm LG (1993) Monitoring of hearing during treatment of leukemia with special reference to the use of amikacin. J\u00a0Intern Med 233:401\u2013407","journal-title":"J Intern Med"},{"key":"663_CR5","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1097\/00129492-200407000-00025","volume":"25","author":"FO Black","year":"2004","unstructured":"Black FO, Pesznecker S, Stallings V (2004) Permanent gentamicin vestibulotoxicity. Otol Neurootol 25:559\u2013569","journal-title":"Otol Neurootol"},{"key":"663_CR6","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1038\/s41467-017-01837-1","volume":"8","author":"AM Breglio","year":"2017","unstructured":"Breglio AM, Rusheen AE, Shide ED, Fernandez KA, Spielbauer KK, McLachlin KM, Hall MD, Amable L, Cunningham L (2017) Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun 8:1654\u20131663","journal-title":"Nat Commun"},{"key":"663_CR7","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, Rajput K, Roebuck D, Sullivan MJ, Laither V, Ronghe M, Dall\u2019Igna (2018) Sodium thiosulfate for protection from cisplatin-induced gearing loss. N\u00a0Eng J Med 378:2376\u20132385","journal-title":"N Eng J Med"},{"key":"663_CR8","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.2353\/ajpath.2010.090610","volume":"176","author":"G Ciarimboli","year":"2010","unstructured":"Ciarimboli G, Deuster D, Knief A, Sperling M, Holtkamp M, Edemir B, Pavenst\u00e4dt H, Lanvers-Kaminsky C et al (2010) Organic cation transporter 2 mediates cisplatin-induced oto- and nephrotoxicity and is a\u00a0target for protective interventions. Am J Pathol 176:1169\u20131180","journal-title":"Am J Pathol"},{"key":"663_CR9","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/S0378-5955(02)00277-0","volume":"165","author":"A Ekborn","year":"2002","unstructured":"Ekborn A, Laurell G, Johnstr\u00f6m P, Wallin I, Eksborg S, Ehrsson H (2002) D\u2011methionine and cisplatin ototoxicity in the guinea pig: D\u2011methionine influences cisplatin pharmacokinetics. Hear Res 165:53\u201361","journal-title":"Hear Res"},{"key":"663_CR10","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1016\/j.ijporl.2015.05.036","volume":"79","author":"MN El-barbary","year":"2015","unstructured":"El-barbary MN, Ismail RIH, Ibrahim AAA (2015) Gentamicin extended interval regimen and ototoxicity in neonates. Int J Ped Otorhinol 79:1294\u20131298","journal-title":"Int J Ped Otorhinol"},{"key":"663_CR11","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1007\/s00280-011-1656-2","volume":"68","author":"C Engm\u00e9r Berglin","year":"2011","unstructured":"Engm\u00e9r Berglin C, Pierre PV, Bramer T, Edsman K, Ehrsson H, Eksborg S, Laurell G (2011) Prevention of cisplatin-induced hearing loss by administration of thisosulfate-containing gel to the middle ear in a\u00a0guinea pig model. Cancer Chemother Pharmacol 68:1547\u20131556","journal-title":"Cancer Chemother Pharmacol"},{"key":"663_CR12","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3109\/00016488709124983","volume":"436","author":"B Engstr\u00f6m","year":"1987","unstructured":"Engstr\u00f6m B, Hillerdal M, Laurell G, Bagger-Sj\u00f6b\u00e4ck D (1987) Selected pathological findings in the human cochlea. Acta Otolaryngol Suppl 436:110\u2013116","journal-title":"Acta Otolaryngol Suppl"},{"key":"663_CR13","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/sj.ki.5002295","volume":"72","author":"L Feldman","year":"2007","unstructured":"Feldman L, Efrati S, Eviatar E, Abrasohn R, Yarovoy I, Gersch E, Averbukh Z, Weissgarten (2007) Gentamicin-induced ototoxicity in hemodialysis patients is ameliorated by N\u2011acetylcysteine. Kidney Int 72:359\u2013363","journal-title":"Kidney Int"},{"key":"663_CR14","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.jcf.2015.06.005","volume":"15","author":"D Fox","year":"2016","unstructured":"Fox D, Cooper MD, Speil CA, Roberts MH, Yanik SC, Meech RP, Hargrove TL et al (2016) D\u2011methionine reduces tobramycin-induced otototoxicity without antimicrobial interference in animal models. J\u00a0Cyst Fibros 15:518\u2013530","journal-title":"J Cyst Fibros"},{"key":"663_CR15","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3389\/fncel.2017.00280","volume":"11","author":"AE Fransson","year":"2017","unstructured":"Fransson AE, Kisiel M, Pirttil\u00e4 K, Pettersson C, Videhult PP, Laurell GFE (2017) Hydrogen inhalation protects against ototoxicity induced by intravenous cisplatin in the guinea pig. Front Cell Neurosci 11:280\u2013292","journal-title":"Front Cell Neurosci"},{"key":"663_CR16","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, Knight K, Villaluna D, Bliss B, Pollock BH, Ramdas J, Lange B, van Hoff D et al (2017) Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer: results from the children\u2019s oncology group ACCL0431 randomised clinical trial. Lancet Oncol 18:63\u201374","journal-title":"Lancet Oncol"},{"key":"663_CR17","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1128\/AAC.2.3.214","volume":"2","author":"RC Gordon","year":"1972","unstructured":"Gordon RC, Regamey C, Kirby WMM (1972) Serum protein binding of the aminoglycoside antibiotics. Antimicrob Agents Chemother 2:214\u2013216","journal-title":"Antimicrob Agents Chemother"},{"key":"663_CR18","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/ppul.23763","volume":"52","author":"JA Handelsman","year":"2017","unstructured":"Handelsman JA, Nasr SZ, Pitts C, King WM (2017) Prevalence of hearing and vestibular loss in cystic fibrosis patients exposed to aminoglycosides. Pediatr Pulmonol 52:1157\u20131162","journal-title":"Pediatr Pulmonol"},{"key":"663_CR19","doi-asserted-by":"publisher","first-page":"3172","DOI":"10.1002\/lary.24235","volume":"123","author":"V Hellberg","year":"2013","unstructured":"Hellberg V, Wallin I, Ehrsson H, Laurell (2013) Cochlear pharmacokientics of cisplatin: an in vivo study in the guinea pig. Laryngoscope 123:3172\u20133177","journal-title":"Laryngoscope"},{"key":"663_CR20","doi-asserted-by":"publisher","first-page":"919","DOI":"10.3109\/00016489.2015.1035797","volume":"135","author":"E Ishikawa","year":"2015","unstructured":"Ishikawa E, Sugimoto H, Hatano M, Nakaishi Y, Tsuji A, Endo K, Kondo S, Wakisaka N, Murono S, Ito M, Yoshizaki T (2015) Protective effects of sodium thiosulfate for cisplatin-mediated ototoxicity in patients with head and neck cancer. Acta Oto Laryngolog 135:919\u2013924","journal-title":"Acta Oto Laryngolog"},{"key":"663_CR21","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1159\/000238762","volume":"36","author":"I Kitasato","year":"1990","unstructured":"Kitasato I, Yokota M, Inouye S, Igarashi M (1990) Comparative ototoxicity of ribostamycin, dactimicin, dibekacin, kanamycin, amikacin, tobramycin, gentamicin, sisomicin and netilmicin in the inner ear of guinea pigs. Chemotherapy 36:155\u2013168","journal-title":"Chemotherapy"},{"key":"663_CR22","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1136\/thoraxjnl-2015-207245","volume":"70","author":"KK Kranzer","year":"2015","unstructured":"Kranzer KK, Elamin WF, Cox H, Seddon JA, Ford N, Drobniewski F (2015) A systematic review and meta-analysis of the efficacy and safety of N\u2011acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug resistant TB. Thorax 70:1070\u20131077","journal-title":"Thorax"},{"key":"663_CR23","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/S0385-8146(04)00147-6","volume":"31","author":"T Kusunoki","year":"2004","unstructured":"Kusunoki T, Cureoglu S, Schachern PA, Sampaio A, Fukushima H, Oktay MF, Paparella MM (2004) Effects of aminoglycoside administration on cochlea elements in human temporal bones. Auris Nasus Larynx 31:383\u2013388","journal-title":"Auris Nasus Larynx"},{"key":"663_CR24","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1093\/jnci\/djn148","volume":"100","author":"BD Lawenda","year":"2008","unstructured":"Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB (2008) Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J\u00a0Natl Cancer Inst 100:773\u2013783","journal-title":"J Natl Cancer Inst"},{"key":"663_CR25","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s00441-016-2359-0","volume":"365","author":"W Liu","year":"2016","unstructured":"Liu W, Edin F, Blom H, Magnusson P, Schrott-Fischer A, Glueckert R, Santi PA, Li H, Laurell G, Rask-Andersen H (2016) Cell Tissue Res 365:13\u201327","journal-title":"Cell. Tissue Res."},{"key":"663_CR26","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1177\/0194599814524894","volume":"150","author":"T Marshak","year":"2014","unstructured":"Marshak T, Steiner M, Kaminer M, Levy L, Shupak A (2014) Prevention of cisplatin-induced hearing loss by intratympanic dexamethasone: a\u00a0randomized controlled study. Head Neck Surg 150:983\u2013990","journal-title":"Head Neck Surg"},{"key":"663_CR27","doi-asserted-by":"publisher","first-page":"9500","DOI":"10.1523\/JNEUROSCI.1544-10.2010","volume":"30","author":"SS More","year":"2010","unstructured":"More SS, Akil O, Ianculescu AG, Geier EG, Lustig RL, Giacomini KM (2010) Role of copper transporter, CTR1, in platinum-induced ototoxicity. J\u00a0Neurosci 30:9500\u20139509","journal-title":"J Neurosci"},{"key":"663_CR28","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1111\/tmi.12608","volume":"20","author":"GM Musiime","year":"2015","unstructured":"Musiime GM, Seale AC, Moxon SG, Lawn JE (2015) Risk of gentamicin toxicity in neonates treated for possible severe bacterial infection in low- and middle-income countries: Systematic review. Trol Med Int Health 20:1593\u20131606","journal-title":"Trol Med Int Health"},{"key":"663_CR29","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1111\/j.1600-0773.1995.tb00167.x","volume":"76","author":"R Ravi","year":"1995","unstructured":"Ravi R, Somani SM, Rybak LP (1995) Mechanisms of cisplatin ototoxicity: antioxidant system. Pharmacol Toxicol 76:386\u2013394","journal-title":"Pharmacol Toxicol"},{"key":"663_CR30","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1159\/000322504","volume":"16","author":"AN Salt","year":"2011","unstructured":"Salt AN, Hartsock J, Plontke S, LeBel C, Piu F (2011) Distribution of dexamethasone and prevention of inner ear function following intratympic delivery of a\u00a0gel-based formulation. Audiol Neurootol 16:323\u2013335","journal-title":"Audiol Neurootol"},{"key":"663_CR31","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.heares.2018.03.002","volume":"368","author":"AN Salt","year":"2018","unstructured":"Salt AN, Plontke SK (2018) Pharmacokinetic principles in the inner ear: Influence of drug properties on intratympanic applications. Hear Res 368:28\u201340","journal-title":"Hear Res"},{"key":"663_CR32","doi-asserted-by":"publisher","first-page":"40","DOI":"10.5935\/0946-5448.20180007","volume":"22","author":"Z Sarafraz","year":"2018","unstructured":"Sarafraz Z, Ahmadi A, Daneshi A (2018) Transtympanic injections of N\u2011acetylcysteine and dexamethasone for prevention of cisplatin-induced ototoxicity: Double blind randomized clinical trial. Int Tinnitus\u00a0J 22:40\u201345","journal-title":"Int Tinnitus J"},{"key":"663_CR33","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1056\/NEJMc053428","volume":"354","author":"SH Sha","year":"2006","unstructured":"Sha SH, Qiu JH, Schacht J (2006) Aspirin to prevent gentamicin-induced hearing loss. N\u00a0Engl J Med 354:1856\u20131857","journal-title":"N Engl J Med"},{"issue":"3","key":"663_CR34","doi-asserted-by":"publisher","first-page":"CD002009","DOI":"10.1002\/14651858","volume":"27","author":"A Smyth","year":"2017","unstructured":"Smyth A, Bhatt J (2017) Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis. Cochrane Database Syst Rev Mar 27(3):CD2009. \n                    https:\/\/doi.org\/10.1002\/14651858","journal-title":"Cochrane Database Syst Rev Mar"},{"key":"663_CR35","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/hed.23551","volume":"37","author":"EAR Theunissen","year":"2015","unstructured":"Theunissen EAR, Bosma SCJ, Zuur CL, Spijker R, van der Baan S, Dreschler WA, de Boer JP, Balm AJM, Rasch CRN (2015) Sensorineural hearing loss in patients with head and neck cancer after chemoradiotherapy and radiotherapy: A systematic review of the literature. Head Neck 37:281\u2013292","journal-title":"Head Neck"},{"issue":"2","key":"663_CR36","doi-asserted-by":"publisher","first-page":"e97","DOI":"10.1097\/MPH.0000000000001282","volume":"41","author":"M Wei","year":"2019","unstructured":"Wei M, Yaun X (2019) Cisplatin-induced ototoxicity in children with solid tumor. J\u00a0Pediatr Hematol Oncol 41(2):e97\u2013e100","journal-title":"J Pediatr Hematol Oncol"}],"container-title":["HNO"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00106-019-0663-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00106-019-0663-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00106-019-0663-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T23:03:19Z","timestamp":1586905399000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00106-019-0663-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,16]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["663"],"URL":"https:\/\/doi.org\/10.1007\/s00106-019-0663-1","relation":{},"ISSN":["0017-6192","1433-0458"],"issn-type":[{"value":"0017-6192","type":"print"},{"value":"1433-0458","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,16]]},"assertion":[{"value":"16 April 2019","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical guidelines"}},{"value":"G.\u00a0Laurell declares that he has no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"For this article no studies with human participants or animals were performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}