Skip to main content
SpringerLink
Log in

Aminoglycoside-Induced Oxidative Stress: Pathways and Protection

  • Chapter
Free Radicals in ENT Pathology

Abstract

The aminoglycosides are life-saving antimicrobials that have the potential to profoundly impair hearing, balance, and renal function. Following initiation of aminoglycoside therapy, reactive oxygen species are generated in the inner ear, often heralding loss of redox homeostasis and ensuing activation of cell death pathways. Experimental models of aminoglycoside ototoxicity have allowed for in-depth study of the underlying mechanisms of oxidative injury to the inner ear and characterization of histopathological and functional correlates. We review the biochemical and molecular underpinnings of aminoglycoside ototoxicity and summarize current approaches to prevention of hearing loss from aminoglycosides. Several potential points of intervention exist, including blocking drug entry into the inner ear and sensory hair cells, mitigating oxidative stress injury, and interfering with inflammatory and cell death pathways. Understanding the pathogenesis of oxidative stress injury and related pathways provides a basis for otoprotective strategies, ranging from use of preventives and rescue agents to rational drug design of non-ototoxic therapeutic aminoglycosides.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alharazneh A, Luk L, Huth M et al (2011) Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity. PLoS One 6(7):e22347. doi:10.1371/journal.pone.0022347

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Arbuzova A, Martushova K, Hangyas-Mihalyne G et al (2000) Fluorescently labeled neomycin as a probe of phosphatidylinositol-4, 5-bisphosphate in membranes. Biochim Biophys Acta 1464(1):35–48

    Article  CAS  PubMed  Google Scholar 

  • Barrangou R (2014) RNA events. Cas9 targeting and the CRISPR revolution. Science 344(6185):707–708. doi:10.1126/science.1252964

    Article  CAS  PubMed  Google Scholar 

  • Battaglia A, Pak K, Brors D, Bodmer D, Frangos JA, Ryan AF (2003) Involvement of ras activation in toxic hair cell damage of the mammalian cochlea. Neuroscience 122(4):1025–1035

    Article  CAS  PubMed  Google Scholar 

  • Behnoud F, Davoudpur K, Goodarzi MT (2009) Can aspirin protect or at least attenuate gentamicin ototoxicity in humans? Saudi Med J 30(9):1165–1169

    PubMed  Google Scholar 

  • Blakley BW, Hochman J, Wellman M, Gooi A, Hussain AE (2008) Differences in ototoxicity across species. J Otolaryngol Head Neck Surg 37(5):700–703

    PubMed  Google Scholar 

  • Bodmer D, Brors D, Pak K, Gloddek B, Ryan A (2002) Rescue of auditory hair cells from aminoglycoside toxicity by Clostridium difficile toxin B, an inhibitor of the small GTPases Rho/Rac/Cdc42. Hear Res 172(1–2):81–86

    Article  CAS  PubMed  Google Scholar 

  • Centers for Disease Control & Prevention (2004) Economic costs associated with mental retardation, cerebral palsy, hearing loss, and vision impairment–United States, 2003. MMWR Morb Mortal Wkly Rep 53(3):57–59

    Google Scholar 

  • Chen Y, Huang WG, Zha DJ et al (2007) Aspirin attenuates gentamicin ototoxicity: from the laboratory to the clinic. Hear Res 226(1–2):178–182. doi:10.1016/j.heares.2006.05.008

    Article  CAS  PubMed  Google Scholar 

  • Chen FQ, Schacht J, Sha SH (2009) Aminoglycoside-induced histone deacetylation and hair cell death in the mouse cochlea. J Neurochem 108(5):1226–1236. doi:10.1111/j.1471-4159.2009.05871.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cheng AG, Cunningham LL, Rubel EW (2005) Mechanisms of hair cell death and protection. Curr Opin Otolaryngol Head Neck Surg 13(6):343–348

    Article  PubMed  Google Scholar 

  • Clerici WJ, Hensley K, DiMartino DL, Butterfield DA (1996) Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res 98(1–2):116–124

    Article  CAS  PubMed  Google Scholar 

  • Comroe JH Jr (1978) Pay dirt: the story of streptomycin. Part I. From Waksman to Waksman. Am Rev Respir Dis 117(4):773–781

    CAS  PubMed  Google Scholar 

  • Cunningham LL, Cheng AG, Rubel EW (2002) Caspase activation in hair cells of the mouse utricle exposed to neomycin. J Neurosci 22(19):8532–8540

    CAS  PubMed  Google Scholar 

  • Cunningham LL, Matsui JI, Warchol ME, Rubel EW (2004) Overexpression of Bcl-2 prevents neomycin-induced hair cell death and caspase-9 activation in the adult mouse utricle in vitro. J Neurobiol 60(1):89–100. doi:10.1002/neu.20006

    Article  CAS  PubMed  Google Scholar 

  • Dai CF, Mangiardi D, Cotanche DA, Steyger PS (2006) Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo. Hear Res 213(1–2):64–78, Epub 2006 Feb 8

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Darrouzet J, Guilhaume A (1974) Ototoxicity of kanamycin studied day by day. Experimental electron microscopic study. Rev Laryngol Otol Rhinol (Bord) 95(9–10):601–621

    CAS  Google Scholar 

  • Davis JM, Elfenbein J, Schum R, Bentler RA (1986) Effects of mild and moderate hearing impairments on language, educational, and psychosocial behavior of children. J Speech Hear Disord 51(1):53–62

    Article  CAS  PubMed  Google Scholar 

  • de Groot JC, Meeuwsen F, Ruizendaal WE, Veldman JE (1990) Ultrastructural localization of gentamicin in the cochlea. Hear Res 50(1–2):35–42

    Article  PubMed  Google Scholar 

  • Dehne N, Rauen U, de Groot H, Lautermann J (2002) Involvement of the mitochondrial permeability transition in gentamicin ototoxicity. Hear Res 169(1–2):47–55

    Article  CAS  PubMed  Google Scholar 

  • Ding D, Stracher A, Salvi RJ (2002) Leupeptin protects cochlear and vestibular hair cells from gentamicin ototoxicity. Hear Res 164(1–2):115–126

    Article  CAS  PubMed  Google Scholar 

  • Duggal P, Sarkar M (2007) Audiologic monitoring of multi-drug resistant tuberculosis patients on aminoglycoside treatment with long term follow-up. BMC Ear Nose Throat Disord 7:5. doi:10.1186/1472-6815-7-5

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Dulon D, Aran JM, Zajic G, Schacht J (1986) Comparative uptake of gentamicin, netilmicin, and amikacin in the guinea pig cochlea and vestibule. Antimicrob Agents Chemother 30(1):96–100

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dulon D, Zajic G, Aran JM, Schacht J (1989) Aminoglycoside antibiotics impair calcium entry but not viability and motility in isolated cochlear outer hair cells. J Neurosci Res 24(2):338–346. doi:10.1002/jnr.490240226

    Article  CAS  PubMed  Google Scholar 

  • Dulon D, Hiel H, Aurousseau C, Erre JP, Aran JM (1993) Pharmacokinetics of gentamicin in the sensory hair cells of the organ of Corti: rapid uptake and long term persistence. C R Acad Sci III 316(7):682–687

    CAS  PubMed  Google Scholar 

  • Elfenbein JL, Hardin-Jones MA, Davis JM (1994) Oral communication skills of children who are hard of hearing. J Speech Hear Res 37(1):216–226

    Article  CAS  PubMed  Google Scholar 

  • Eshraghi AA, Hoosien G, Ramsay S et al (2010) Inhibition of the JNK signal cascade conserves hearing against electrode insertion trauma-induced loss. Cochlear Implants Int 11(suppl 1):104–109. doi:10.1179/146701010X12671177544104

    Article  PubMed  Google Scholar 

  • Estivill X, Govea N, Barcelo E et al (1998) Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides. Am J Hum Genet 62:27–35

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, McDonald WJ (1992) High-frequency audiometric monitoring for early detection of aminoglycoside ototoxicity. J Infect Dis 165(6):1026–1032

    Article  CAS  PubMed  Google Scholar 

  • Fee WE Jr (1980) Aminoglycoside ototoxicity in the human. Laryngoscope 90(10 pt 2 suppl 24):1–19

    Article  PubMed  Google Scholar 

  • Feldman L, Efrati S, Eviatar E et al (2007) Gentamicin-induced ototoxicity in hemodialysis patients is ameliorated by N-acetylcysteine. Kidney Int 72(3):359–363. doi:10.1038/sj.ki.5002295

    Article  CAS  PubMed  Google Scholar 

  • Fetoni AR, Sergi B, Ferraresi A, Paludetti G, Troiani D (2004) alpha-Tocopherol protective effects on gentamicin ototoxicity: an experimental study. Int J Audiol 43(3):166–171

    Article  PubMed  Google Scholar 

  • Fischel-Ghodsian N (2005) Genetic factors in aminoglycoside toxicity. Pharmacogenomics 6(1):27–36. doi:10.1517/14622416.6.1.27

    Article  CAS  PubMed  Google Scholar 

  • Forge A, Fradis M (1985) Structural abnormalities in the stria vascularis following chronic gentamicin treatment. Hear Res 20(3):233–244

    Article  CAS  PubMed  Google Scholar 

  • Forge A, Schacht J (2000) Aminoglycoside antibiotics. Audiol Neurootol 5(1):3–22

    Article  CAS  PubMed  Google Scholar 

  • Forge A, Li L, Corwin JT, Nevill G (1993) Ultrastructural evidence for hair cell regeneration in the mammalian inner ear. Science 259(5101):1616–1619

    Article  CAS  PubMed  Google Scholar 

  • Forge A, Li L, Nevill G (1998) Hair cell recovery in the vestibular sensory epithelia of mature guinea pigs. J Comp Neurol 397(1):69–88

    Article  CAS  PubMed  Google Scholar 

  • Garetz SL, Altschuler RA, Schacht J (1994) Attenuation of gentamicin ototoxicity by glutathione in the guinea pig in vivo. Hear Res 77(1–2):81–87

    Article  CAS  PubMed  Google Scholar 

  • Gatell JM, Ferran F, Araujo V et al (1987) Univariate and multivariate analyses of risk factors predisposing to auditory toxicity in patients receiving aminoglycosides. Antimicrob Agents Chemother 31(9):1383–1387

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Govaerts PJ, Claes J, van de Heyning PH, Jorens PG, Marquet J, De Broe ME (1990) Aminoglycoside-induced ototoxicity. Toxicol Lett 52(3):227–251

    Article  CAS  PubMed  Google Scholar 

  • Grohskopf LA, Huskins WC, Sinkowitz-Cochran RL et al (2005) Use of antimicrobial agents in United States neonatal and pediatric intensive care patients. Pediatr Infect Dis J 24(9):766–773

    Article  PubMed  Google Scholar 

  • Hainrichson M, Nudelman I, Baasov T (2008) Designer aminoglycosides: the race to develop improved antibiotics and compounds for the treatment of human genetic diseases. Org Biomol Chem 6(2):227–239. doi:10.1039/b712690p

    Article  CAS  PubMed  Google Scholar 

  • Harvey SC, Li X, Skolnick P, Kirst HA (2000) The antibacterial and NMDA receptor activating properties of aminoglycosides are dissociable. Eur J Pharmacol 387(1):1–7

    Article  CAS  PubMed  Google Scholar 

  • Hashino E, Shero M, Salvi RJ (1997) Lysosomal targeting and accumulation of aminoglycoside antibiotics in sensory hair cells. Brain Res 777(1–2):75–85

    Article  CAS  PubMed  Google Scholar 

  • Hawkins E Jr (1973) Ototoxic mechanisms. A working hypothesis. Audiology 12(5):383–393

    Article  PubMed  Google Scholar 

  • Hawkins JE (1976) Drug ototoxicity. In: Keidel WD, Neff WD (eds) Handbook of sensory physiology, vol 5. Springer, Berlin, pp 707–748

    Google Scholar 

  • Henley CM III, Schacht J (1988) Pharmacokinetics of aminoglycoside antibiotics in blood, inner-ear fluids and tissues and their relationship to ototoxicity. Audiology 27(3):137–146

    Article  PubMed  Google Scholar 

  • Hennig S, McKay K, Vidmar S, O’Brien K, Stacey S, Cheney J, Wainwright CE (2014) Safety of inhaled (TOBI) and intravenous tobramycin in young children with cystic fibrosis. J Cyst Fibros 13:428–434

    Article  CAS  PubMed  Google Scholar 

  • Hiel H, Bennani H, Erre JP, Aurousseau C, Aran JM (1992) Kinetics of gentamicin in cochlear hair cells after chronic treatment. Acta Otolaryngol 112(2):272–277

    CAS  PubMed  Google Scholar 

  • Hinojosa R, Lerner SA (1987) Cochlear neural degeneration without hair cell loss in two patients with aminoglycoside ototoxicity. J Infect Dis 156(3):449–455

    Article  CAS  PubMed  Google Scholar 

  • Hinshaw HC, Feldman DVM (1945) Streptomycin in treatment of clinical tuberculosis: a preliminary report. Proc Staff Meet Mayo Clin 20:313–318

    Google Scholar 

  • Hirose K, Hockenbery DM, Rubel EW (1997) Reactive oxygen species in chick hair cells after gentamicin exposure in vitro. Hear Res 104(1–2):1–14

    Article  CAS  PubMed  Google Scholar 

  • Horvath P, Barrangou R (2010) CRISPR/Cas, the immune system of bacteria and archaea. Science 327(5962):167–170. doi:10.1126/science.1179555

    Article  CAS  PubMed  Google Scholar 

  • Houghton JL, Green KD, Chen W, Garneau-Tsodikova S (2010) The future of aminoglycosides: the end or renaissance? Chembiochem 11(7):880–902. doi:10.1002/cbic.200900779

    Article  CAS  PubMed  Google Scholar 

  • Imamura S, Adams JC (2003) Distribution of gentamicin in the guinea pig inner ear after local or systemic application. J Assoc Res Otolaryngol 4(2):176–195. doi:10.1007/s10162-002-2036-8

    Article  PubMed Central  PubMed  Google Scholar 

  • Jiang H, Sha SH, Schacht J (2005) NF-kappaB pathway protects cochlear hair cells from aminoglycoside-induced ototoxicity. J Neurosci Res 79(5):644–651. doi:10.1002/jnr.20392

    Article  CAS  PubMed  Google Scholar 

  • Jiang H, Sha SH, Forge A, Schacht J (2006a) Caspase-independent pathways of hair cell death induced by kanamycin in vivo. Cell Death Differ 13(1):20–30. doi:10.1038/sj.cdd.4401706

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jiang H, Sha SH, Schacht J (2006b) Kanamycin alters cytoplasmic and nuclear phosphoinositide signaling in the organ of Corti in vivo. J Neurochem 99(1):269–276. doi:10.1111/j.1471-4159.2006.04117.x

    Article  CAS  PubMed  Google Scholar 

  • Jiang H, Sha SH, Schacht J (2006c) Rac/Rho pathway regulates actin depolymerization induced by aminoglycoside antibiotics. J Neurosci Res 83(8):1544–1551. doi:10.1002/jnr.20833

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kalghatgi S, Spina CS, Costello JC et al (2013) Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in mammalian cells. Sci Transl Med 5(192):192ra85. doi:10.1126/scitranslmed.3006055

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kaufman RJ (1999) Correction of genetic disease by making sense from nonsense. J Clin Invest 104(4):367–368. doi:10.1172/JCI8055

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kawaguchi H, Naito T, Nakagawa S, Fujisawa KI (1972) BB-K 8, a new semisynthetic aminoglycoside antibiotic. J Antibiot (Tokyo) 25:695–708

    Article  CAS  Google Scholar 

  • Kawai Y, Kohda Y, Kodawara T, Gemba M (2005) Protective effect of a protein kinase inhibitor on cellular injury induced by cephaloridine in the porcine kidney cell line LLC-PK(1). J Toxicol Sci 30(3):157–163

    Article  CAS  PubMed  Google Scholar 

  • Kharkheli E, Kevanishvili Z, Maglakelidze T, Davitashvili O, Schacht J (2007) Does vitamin E prevent gentamicin-induced ototoxicity? Georgian Med News 146:14–17

    PubMed  Google Scholar 

  • Komune S, Ide M, Nakano T, Morimitsu T (1987) Effects of kanamycin sulfate on cochlear potentials and potassium ion permeability through the cochlear partitions. ORL J Otorhinolaryngol Relat Spec 49(1):9–16

    Article  CAS  PubMed  Google Scholar 

  • Konstan MW, Flume PA, Kappler M, Chiron R, Higgins M, Brockhaus F, Zhang J, Angyalosi G, He E, Geller DE (2011) Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: the EAGER trial. J Cyst Fibros 10:54–61

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ladrech S, Guitton M, Saido T, Lenoir M (2004) Calpain activity in the amikacin-damaged rat cochlea. J Comp Neurol 477(2):149–160. doi:10.1002/cne.20252

    Article  CAS  PubMed  Google Scholar 

  • Lautermann J, McLaren J, Schacht J (1995) Glutathione protection against gentamicin ototoxicity depends on nutritional status. Hear Res 86(1–2):15–24

    Article  CAS  PubMed  Google Scholar 

  • Le Prell CG, Ojano-Dirain C, Rudnick EW, Nelson MA, DeRemer SJ, Prieskorn DM, Miller JM (2014) Assessment of nutrient supplement to reduce gentamicin-induced ototoxicity. J Assoc Res Otolaryngol 15(3):375–393

    PubMed Central  PubMed  Google Scholar 

  • Leake PA, Hradek GT (1988) Cochlear pathology of long term neomycin induced deafness in cats. Hear Res 33(1):11–33

    Article  CAS  PubMed  Google Scholar 

  • Leitner MG, Halaszovich CR, Oliver D (2011) Aminoglycosides inhibit KCNQ4 channels in cochlear outer hair cells via depletion of phosphatidylinositol(4,5)bisphosphate. Mol Pharmacol 79(1):51–60. doi:10.1124/mol.110.068130

    Article  CAS  PubMed  Google Scholar 

  • Lesniak W, Pecoraro VL, Schacht J (2005) Ternary complexes of gentamicin with iron and lipid catalyze formation of reactive oxygen species. Chem Res Toxicol 18(2):357–364. doi:10.1021/tx0496946

    Article  CAS  PubMed  Google Scholar 

  • Li H, Steyger PS (2009) Synergistic ototoxicity due to noise exposure and aminoglycoside antibiotics. Noise Health 11(42):26–32

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li H, Wang Q, Steyger PS (2011) Acoustic trauma increases cochlear and hair cell uptake of gentamicin. PLoS One 6(4):e19130. doi:10.1371/journal.pone.0019130

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lim DJ (1986) Effects of noise and ototoxic drugs at the cellular level in the cochlea: a review. Am J Otolaryngol 7:73–99

    Article  CAS  PubMed  Google Scholar 

  • Lindeman HH (1969) Regional differences in sensitivity of the vestibular sensory epithelia to ototoxic antibiotics. Acta Otolaryngol 67(2):177–189

    Article  CAS  PubMed  Google Scholar 

  • Liu K, Jiang X, Shi C et al (2013) Cochlear inner hair cell ribbon synapse is the primary target of ototoxic aminoglycoside stimuli. Mol Neurobiol 48(3):647–654. doi:10.1007/s12035-013-8454-2

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ (2011) New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int 79(1):33–45. doi:10.1038/ki.2010.337

    Article  CAS  PubMed  Google Scholar 

  • Malik V, Rodino-Klapac LR, Viollet L, Mendell JR (2010) Aminoglycoside-induced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy. Ther Adv Neurol Disord 3(6):379–389. doi:10.1177/1756285610388693

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mangiardi DA, McLaughlin-Williamson K, May KE, Messana EP, Mountain DC, Cotanche DA (2004) Progression of hair cell ejection and molecular markers of apoptosis in the avian cochlea following gentamicin treatment. J Comp Neurol 475(1):1–18. doi:10.1002/cne.20129

    Article  CAS  PubMed  Google Scholar 

  • Marcotti W, van Netten SM, Kros CJ (2005) The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano-electrical transducer channels. J Physiol 567(Pt 2):505–521. doi:10.1113/jphysiol.2005.085951

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maroney AC, Glicksman MA, Basma AN et al (1998) Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway. J Neurosci 18(1):104–111

    CAS  PubMed  Google Scholar 

  • Mathog RH, Klein WJ Jr (1969) Ototoxicity of ethacrynic acid and aminoglycoside antibiotics in uremia. N Engl J Med 280(22):1223–1224. doi:10.1056/NEJM196905292802208

    Article  CAS  PubMed  Google Scholar 

  • Matsui JI, Gale JE, Warchol ME (2004) Critical signaling events during the aminoglycoside-induced death of sensory hair cells in vitro. J Neurobiol 61(2):250–266. doi:10.1002/neu.20054

    Article  CAS  PubMed  Google Scholar 

  • Matt T, Ng CL, Lang K et al (2012) Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin. Proc Natl Acad Sci U S A 109(27):10984–10989. doi:10.1073/pnas.1204073109

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Matz GJ (1993) Aminoglycoside cochlear ototoxicity. Otolaryngol Clin North Am 26:705–712

    CAS  PubMed  Google Scholar 

  • Metcalfe NH (2011) Sir Geoffrey Marshall (1887–1982): respiratory physician, catalyst for anaesthesia development, doctor to both Prime Minster and King, and World War I Barge Commander. J Med Biogr 19(1):10–14. doi:10.1258/jmb.2010.010019

    Article  PubMed  Google Scholar 

  • Mizuta K, Saito A, Watanabe T et al (1999) Ultrastructural localization of megalin in the rat cochlear duct. Hear Res 129(1–2):83–91

    Article  CAS  PubMed  Google Scholar 

  • Moestrup SK, Cui S, Vorum H et al (1995) Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs. J Clin Invest 96(3):1404–1413. doi:10.1172/JCI118176

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mohtat D, Susztak K (2010) Fine tuning gene expression: the epigenome. Semin Nephrol 30(5):468–476. doi:10.1016/j.semnephrol.2010.07.004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Momiyama J, Hashimoto T, Matsubara A, Futai K, Namba A, Shinkawa H (2006) Leupeptin, a calpain inhibitor, protects inner ear hair cells from aminoglycoside ototoxicity. Tohoku J Exp Med 209(2):89–97

    Article  CAS  PubMed  Google Scholar 

  • Moore RD, Smith CR, Lietman PS (1984) Risk factors for the development of auditory toxicity in patients receiving aminoglycosides. J Infect Dis 149(1):23–30

    Article  CAS  PubMed  Google Scholar 

  • Nadol JB Jr (1997) Patterns of neural degeneration in the human cochlea and auditory nerve: implications for cochlear implantation. Otolaryngol Head Neck Surg 117(3 Pt 1):220–228

    Article  PubMed  Google Scholar 

  • Nakagawa T, Yamane H, Takayama M, Sunami K, Nakai Y (1998) Apoptosis of guinea pig cochlear hair cells following chronic aminoglycoside treatment. Eur Arch Otorhinolaryngol 255(3):127–131

    Article  CAS  PubMed  Google Scholar 

  • Nudelman I, Rebibo-Sabbah A, Cherniavsky M et al (2009) Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations. J Med Chem 52(9):2836–2845. doi:10.1021/jm801640k

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ou HC, Raible DW, Rubel EW (2007) Cisplatin-induced hair cell loss in zebrafish (Danio rerio) lateral line. Hear Res 233(1–2):46–53. doi:10.1016/j.heares.2007.07.003

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ou H, Simon JA, Rubel EW, Raible DW (2012) Screening for chemicals that affect hair cell death and survival in the zebrafish lateral line. Hear Res 288(1–2):58–66. doi:10.1016/j.heares.2012.01.009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pfannenstiel SC, Praetorius M, Plinkert PK, Brough DE, Staecker H (2009) Bcl-2 gene therapy prevents aminoglycoside-induced degeneration of auditory and vestibular hair cells. Audiol Neurootol 14(4):254–266. doi:10.1159/000192953

    Article  CAS  PubMed  Google Scholar 

  • Pirvola U, Xing-Qun L, Virkkala J et al (2000) Rescue of hearing, auditory hair cells, and neurons by CEP-1347/KT7515, an inhibitor of c-Jun N-terminal kinase activation. J Neurosci 20(1):43–50

    CAS  PubMed  Google Scholar 

  • Poirrier AL, Van den Ackerveken P, Kim TS, Vandenbosch R, Nguyen L, Lefebvre PP, Malgrange B (2010) Ototoxic drugs: difference in sensitivity between mice and guinea pigs. Toxicol Lett 193(1):41–49. doi:10.1016/j.toxlet.2009.12.003

    Article  CAS  PubMed  Google Scholar 

  • Pong AL, Bradley JS (2005) Guidelines for the selection of antibacterial therapy in children. Pediatr Clin North Am 52(3):869–894, viii. doi:10.1016/j.pcl.2005.02.008

    Google Scholar 

  • Prezant TR, Agapian JV, Bohlman MC et al (1993) Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet 4(3):289–294. doi:10.1038/ng0793-289

    Article  CAS  PubMed  Google Scholar 

  • Raphael Y, Fein A, Nebel L (1983) Transplacental kanamycin ototoxicity in the guinea pig. Arch Otorhinolaryngol 238(1):45–51

    Article  CAS  PubMed  Google Scholar 

  • Richardson GP, Forge A, Kros CJ, Fleming J, Brown SD, Steel KP (1997) Myosin VIIA is required for aminoglycoside accumulation in cochlear hair cells. J Neurosci 17(24):9506–9519

    CAS  PubMed  Google Scholar 

  • Ruedi L, Furrer W, Luthy F, Nager G, Tschirren B (1952) Further observations concerning the toxic effects of streptomycin and quinine on the auditory organ of guinea pigs. Laryngoscope 62(4):333–351. doi:10.1288/00005537-195204000-00001

    Article  CAS  PubMed  Google Scholar 

  • Rybak LP, Brenner MJ (2014) Vestibular and auditory ototoxicity (Chapter 154). In: Flint PW et al (eds) Cummings otolaryngology: head and neck surgery, vol III, 6th edn. Elsevier, Philadelphia, pp 2369–2382

    Google Scholar 

  • Rybak LP, Ramkumar V (2007) Ototoxicity. Kidney Int 72(8):931–935. doi:10.1038/sj.ki.5002434

    Article  CAS  PubMed  Google Scholar 

  • Rybak LP, Brenner MJ (2014) Vestibular and Auditory Ototoxicity Chapter 154. Cummings Otolaryngology: Head and Neck surgery. 2014. 6th Ed Philadelphia, PA. Elsevier. Volume III. 2369–2382

    Google Scholar 

  • Santos F, MacDonald G, Rubel EW, Raible DW (2006) Lateral line hair cell maturation is a determinant of aminoglycoside susceptibility in zebrafish (Danio rerio). Hear Res 213(1–2):25–33. doi:10.1016/j.heares.2005.12.009

    Article  CAS  PubMed  Google Scholar 

  • Schacht J (1979) Isolation of an aminoglycoside receptor from guinea pig inner ear tissues and kidney. Arch Otorhinolaryngol 224(1–2):129–134

    Article  CAS  PubMed  Google Scholar 

  • Schacht J, Talaska AE, Rybak LP (2008) Drug-induced hearing loss. In: Schacht J, Popper AN, Fay RR (eds) Auditory trauma, protection, and repair. Springer, New York, pp 219–256

    Chapter  Google Scholar 

  • Schacht J, Talaska AE, Rybak LP (2012) Cisplatin and aminoglycoside antibiotics: hearing loss and its prevention. Anat Rec 295(11):1837–1850

    Article  CAS  Google Scholar 

  • Schatz A, Bugie E, Waksman SA (1944) Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc Soc Exp Biol Med 55:66–69

    Article  CAS  Google Scholar 

  • Schmitt NC, Rubel EW, Nathanson NM (2009) Cisplatin-induced hair cell death requires STAT1 and is attenuated by epigallocatechin gallate. J Neurosci 29(12):3843–3851. doi:10.1523/JNEUROSCI. 5842-08.2009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sha SH, Schacht J (1999a) Formation of reactive oxygen species following bioactivation of gentamicin. Free Radic Biol Med 26(3–4):341–347

    Article  CAS  PubMed  Google Scholar 

  • Sha SH, Schacht J (1999b) Salicylate attenuates gentamicin-induced ototoxicity. Lab Invest 79(7):807–813

    CAS  PubMed  Google Scholar 

  • Sha SH, Schacht J (2000) Antioxidants attenuate gentamicin-induced free radical formation in vitro and ototoxicity in vivo: D-methionine is a potential protectant. Hear Res 142:34–40

    Article  CAS  PubMed  Google Scholar 

  • Sha SH, Zajic G, Epstein CJ, Schacht J (2001) Overexpression of copper/zinc-superoxide dismutase protects from kanamycin-induced hearing loss. Audiol Neurootol 6(3):117–123

    Article  CAS  PubMed  Google Scholar 

  • Sha SH, Qiu JH, Schacht J (2006) Aspirin to prevent gentamicin-induced hearing loss. N Engl J Med 354(17):1856–1857. doi:10.1056/NEJMc053428

    Article  CAS  PubMed  Google Scholar 

  • Shimizu A, Takumida M, Anniko M, Suzuki M (2003) Calpain and caspase inhibitors protect vestibular sensory cells from gentamicin ototoxicity. Acta Otolaryngol 123(4):459–465

    Article  CAS  PubMed  Google Scholar 

  • Shulman E, Belakhov V, Wei G et al (2014) Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosomes show decreased ototoxicity: a strategy for the treatment of genetic diseases. J Biol Chem 289(4):2318–2330

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sone M, Schachern PA, Paparella MM (1998) Loss of spiral ganglion cells as primary manifestation of aminoglycoside ototoxicity. Hear Res 115(1–2):217–223

    Article  CAS  PubMed  Google Scholar 

  • Staecker H, Kopke R, Malgrange B, Lefebvre P, Van de Water TR (1996) NT-3 and/or BDNF therapy prevents loss of auditory neurons following loss of hair cells. Neuroreport 7(4):889–894

    Article  CAS  PubMed  Google Scholar 

  • Staecker H, Liu W, Malgrange B, Lefebvre PP, Van De Water TR (2007) Vector-mediated delivery of bcl-2 prevents degeneration of auditory hair cells and neurons after injury. ORL J Otorhinolaryngol Relat Spec 69(1):43–50. doi:10.1159/000096716

    Article  CAS  PubMed  Google Scholar 

  • Stepanyan RS, Indzhykulian AA, Velez-Ortega AC et al (2011) TRPA1-mediated accumulation of aminoglycosides in mouse cochlear outer hair cells. J Assoc Res Otolaryngol 12(6):729–740. doi:10.1007/s10162-011-0288-x

    Article  PubMed Central  PubMed  Google Scholar 

  • Steyger PS, Peters SL, Rehling J, Hordichok A, Dai CF (2003) Uptake of gentamicin by bullfrog saccular hair cells in vitro. J Assoc Res Otolaryngol 4(4):565–578, Epub 2003 Nov 12

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tabuchi K, Pak K, Chavez E, Ryan AF (2007) Role of inhibitor of apoptosis protein in gentamicin-induced cochlear hair cell damage. Neuroscience 149(1):213–222. doi:10.1016/j.neuroscience.2007.06.061

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi T, Hikiti T, Nitta K (1957) Studies on kanamycin. J Antibiot (Tokyo) 10:107–114

    CAS  Google Scholar 

  • Taylor RR, Nevill G, Forge A (2008) Rapid hair cell loss: a mouse model for cochlear lesions. J Assoc Res Otolaryngol 9(1):44–64

    Article  PubMed Central  PubMed  Google Scholar 

  • Thompson RQ, Presti EA (1967) Nebramycin, a new broad-spectrum antibiotic complex. 3. Isolation and chemical-physical properties. Antimicrob Agents Chemother (Bethesda) 7:332–340

    CAS  Google Scholar 

  • Tono T, Kiyomizu K, Matsuda K et al (2001) Different clinical characteristics of aminoglycoside-induced profound deafness with and without the 1555 A→G mitochondrial mutation. ORL J Otorhinolaryngol Relat Spec 63(1):25–30

    Article  CAS  PubMed  Google Scholar 

  • Tran Ba Huy P, Bernard P, Schacht J (1986) Kinetics of gentamicin uptake and release in the rat. Comparison of inner ear tissues and fluids with other organs. J Clin Invest 77(5):1492–1500. doi:10.1172/JCI112463

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • van Ruijven MW, de Groot JC, Klis SF, Smoorenburg GF (2005) The cochlear targets of cisplatin: an electrophysiological and morphological time-sequence study. Hear Res 205(1–2):241–248. doi:10.1016/j.heares.2005.03.023

    Article  PubMed  CAS  Google Scholar 

  • Wagner KR, Hamed S, Hadley DW et al (2001) Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations. Ann Neurol 49(6):706–711

    Article  CAS  PubMed  Google Scholar 

  • Waksman SA, Lechavalier H (1949) Neomycin, a new antibiotic active against streptomycin resistant bacteria, including tuberculosis organisms. Science 109:305–307

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Van De Water TR, Bonny C, de Ribaupierre F, Puel JL, Zine A (2003) A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. J Neurosci 23(24):8596–8607

    CAS  PubMed  Google Scholar 

  • Webster M, Webster DB (1981) Spiral ganglion neuron loss following organ of Corti loss: a quantitative study. Brain Res 212(1):17–30

    Article  CAS  PubMed  Google Scholar 

  • Weinstein M, Luedemann GM, Oden EM, Wagman GH, Rosselet JP, Marquez JA, Coniglio CT, Charney W, Herzog H, Black J (1963) Gentamicin, a new antimicrobial complex from micromonospora. J Med Chem 6:463–464

    Article  CAS  PubMed  Google Scholar 

  • Wiedenheft B, Sternberg SH, Doudna JA (2012) RNA-guided genetic silencing systems in bacteria and archaea. Nature 482(7385):331–338. doi:10.1038/nature10886

    Article  CAS  PubMed  Google Scholar 

  • Williams JA, Holder N (2000) Cell turnover in neuromasts of zebrafish larvae. Hear Res 143(1–2):171–181

    Article  CAS  PubMed  Google Scholar 

  • Williams SE, Smith DE, Schacht J (1987) Characteristics of gentamicin uptake in the isolated crista ampullaris of the inner ear of the guinea pig. Biochem Pharmacol 36(1):89–95

    Article  CAS  PubMed  Google Scholar 

  • Wu WJ, Sha SH, McLaren JD, Kawamoto K, Raphael Y, Schacht J (2001) Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague–Dawley rat. Hear Res 158:165–178

    Article  CAS  PubMed  Google Scholar 

  • Xie J, Talaska AE, Schacht J (2011) New developments in aminoglycoside therapy and ototoxicity. Hear Res 281(1–2):28–37. doi:10.1016/j.heares.2011.05.008

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ylikoski J, Xing-Qun L, Virkkala J, Pirvola U (2002) Blockade of c-Jun N-terminal kinase pathway attenuates gentamicin-induced cochlear and vestibular hair cell death. Hear Res 166(1–2):33–43

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Otolaryngology—Head & Neck Surgery, Departments of Surgery and Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA

    Leonard P. Rybak M.D., Ph.D.

  2. Department of Otolaryngology—Head & Neck Surgery, Kresge Hearing Research Institute, University of Michigan School of Medicine, 1150 W. Medical Center Drive Room 5416 Med Sci II, Ann Arbor, MI, 48109-5616, USA

    Michael J. Brenner M.D.

Authors
  1. Leonard P. Rybak M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael J. Brenner M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael J. Brenner M.D. .

Editor information

Editors and Affiliations

  1. Cochlear Signaling & Tissue Engin., University of Michigan Kresge Hearing Research Institute, Ann Arbor, Michigan, USA

    Josef Miller

  2. Dept of Speech , Lang & Hearing Sci, Univ of Florida Health Sciences Center, Gainesville, Florida, USA

    Colleen G. Le Prell

  3. Div . of Otolaryngology Head & Neck Surgery, SIU School of Medicine, Springfield, Illinois, USA

    Leonard Rybak

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Rybak, L.P., Brenner, M.J. (2015). Aminoglycoside-Induced Oxidative Stress: Pathways and Protection. In: Miller, J., Le Prell, C., Rybak, L. (eds) Free Radicals in ENT Pathology. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Cham. https://doi.org/10.1007/978-3-319-13473-4_10

Download citation

Publish with us

Policies and ethics

Search

Navigation