Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Review

Aminoglycoside Antibiotics

Forge A.a · Schacht J.b

Author affiliations

aInstitute of Laryngology and Otology, University College London, UK; bKresge Hearing Research Institute, Ann Arbor, Mich., USA

Related Articles for ""

Audiol Neurootol 2000;5:3–22

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.
Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00


Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Review

Published online: February 10, 2000
Issue release date: January – February

Number of Print Pages: 20
Number of Figures: 4
Number of Tables: 2

ISSN: 1420-3030 (Print)
eISSN: 1421-9700 (Online)

For additional information: https://www.karger.com/AUD

Abstract

In the 50 years since their discovery, the aminoglycoside antibiotics have seen unprecedented use. Discovered in the 1940s, they were the long-sought remedy for tuberculosis and other serious bacterial infections. The side effects of renal and auditory toxicity, however, led to a decline of their use in most countries in the 1970s and 1980s. Nevertheless, today the aminoglycosides are still the most commonly used antibiotics worldwide thanks to the combination of their high efficacy with low cost. This review first summarizes the history, chemistry, antibacterial actions and acute side effects of the drugs. It then details the pathophysiology of aminoglycoside ototoxicity including experimental and clinical observations, risk factors and incidence. Pharmacokinetics, cellular actions and our current understanding of the underlying molecular mechanisms of ototoxicity are discussed at length. The review concludes with recent advances towards therapeutic intervention to prevent aminoglycoside ototoxicity.

© 2000 S. Karger AG, Basel


References

  1. Aran JM, Darrouzet J: Observation of click-evoked compound VIII nerve responses before, during, and over seven months after kanamycin treatment in the guinea pig. Acta Otolaryngol (Stockh) 1975;79:24–32.
    External Resources
  2. Aran JM, Dulon D, Hiel H, Erre JP, Aurousseau C: L’ototoxicité d’aminosides: résultats récents sur la captation et la clairance de la gentamicine par les cellules sensorielles du limacon osseux. Rev Laryngol Otol Rhinol (Bord) 1993;114:125–128.
  3. Aruoma OI, Kaur H, Halliwell B: Oxygen free radicals and human diseases. J R Soc Health 1991;111:172–177.
  4. Balogh K, Hiraide F, Ishii D: Distribution of radioactive dihydrostreptomycin in the cochlea. Ann Otol Rhinol 1970;79:641–652.
    External Resources
  5. Barber DA, Harris SR: Oxygen free radicals and antioxidants: A review. Am Pharm 1994;NS34:26–35.
  6. Barton-Davis ER, Cordier L, Shoturma DI, Leland SE, Sweeney HL: Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice. J Clin Invest 1999;375–381.
  7. Basile AS, Huang JM, Xie C, Webster D, Berlin C, Skolnick P: N-Methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss. Nat Med 1996;12:1338–1343.
  8. Bernard PA: Freedom from ototoxicity in aminoglycoside treated neonates: A mistaken notion. Laryngoscope 1981;91:1985–1994.
    External Resources
  9. Bernard PA, Péchère JC, Hébert R: Altered objective audiometry in aminoglycosides-treated human neonates. Arch Otorhinolaryngol 1980;228:205–210.
    External Resources
  10. Blakley BW: Clinical forum: A review of intratympanic therapy. Am J Otol 1997;18:520–526.
  11. Blanchard SC, Fourmy D, Eason RG, Puglisi JD: rRNA chemical groups required for aminoglycoside binding. Biochemistry 1998;37:7716–7724.
    External Resources
  12. Bock GR, Yates GK, Miller JJ, Moorjani P: Effects of N-acetylcysteine on kanamycin ototoxicity in the guinea pig. Hear Res 1983;9:255–262.
  13. Brouet G, Marche J, Chevallier J, Liot F, Le Meur G, Bergogne Mme: Étude expérimentale et clinique de la kanamycine dans l’infection tuberculeuse. Rev Tub Pneum 1959;23:949–988.
  14. Brown AM, McDowell B, Forge A: Acoustic distortion products can be used to monitor the effects of chronic gentamicin treatment. Hear Res 1989;42:143–156.
  15. Brown JJ, Brummett RE, Fox KE, Bendrick TW: Combined effects of noise and kanamycin: Cochlear pathology and pharmacology. Arch Otolaryngol 1980;106:744–750.
    External Resources
  16. Brummet RE, Fox KE: Studies of aminoglycoside ototoxicity in animal models; in Welton A, Neu HC (eds): The Aminoglycosides. Microbiology, Clinical Use and Toxicology. New York, Marcel Dekker Inc., 1982, pp 419–451.
  17. Capps MJ, Duvall AJ: Ototoxicity and the olivocochlear bundle. Laryngoscope 1977;87:1100–1108.
    External Resources
  18. Caussé R, Gondet I, Vallancien B: Action de la streptomycine sur les cellules ciliées des organes vestibulaires de la souris. C R Soc Biol 1949;143:619–620.
  19. Chernov MV, Stark GR: The p53 activation and apoptosis induced by DNA damage are reversibly inhibited by salicylate. Oncogene 1997;14:2503–2510.
    External Resources
  20. Clerici WJ, Hensley K, DiMartino DL, Butterfield DA: Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants. Hear Res 1996;98:116–124.
  21. Conlon BJ, Aran J-M, Erre J-P, Smith, DW: Attenuation of aminoglycoside-induced cochlear damage with the metabolic antioxidant α-lipoic acid. Hear Res 1999;128:40–44.
  22. Conlon BJ, Smith DW: Attenuation of neomycin ototoxicity by iron chelation. Laryngoscope 1998a;108:284–287.
  23. Conlon BJ, Smith DW: Supplemental iron exacerbates aminoglycoside ototoxicity in vivo. Hear Res 1998b;115:1–5.
  24. Corrado AP, de Morais IP, Prado WA: Aminoglycoside antibiotics as a tool for the study of the biological role of calcium ions: Historical overview. Acta Physiol Pharmacol Latinoam 1989;39:419–430.
    External Resources
  25. Crann SA, Huang MY, McLaren JD, Schacht J: Formation of a toxic metabolite from gentamicin by a hepatic cytosolic fraction. Biochem Pharmacol 1992;43:1835–1839.
  26. Darrouzet J, Guilhaume A: Ototoxicité de la kanamycine au jour le jour: Étude expérimentale en microscopie électronique. Rev Laryngol (Bord) 1974;95:601–621.
  27. Davis BD: Mechanism of bactericidal action of aminoglycosides. Microbiol Rev 1987;51:341–350.
  28. Davis H, Deatherage BH, Ronsenblut B, Fernández C, Kimura R, Smith CA: Modification of cochlear potentials produced by streptomycin poisoning and by extensive venous obstruction. Laryngoscope 1958;68:596–627.
  29. De Groot JC, Meeuwsen F, Ruizendaal WE, Veldman JE: Ultrastructural localization of gentamicin in cochlea, Hear Res 1990;50:35–42.
  30. Dinis TC, Maderia VM, Almeida LM: Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch Biochem Biophys 1994;315:161–169.
  31. Duckert LG, Rubel EW: Morphological correlates of functional recovery in the chicken inner ear after gentamicin treatment. J Comp Neurol 1993;331:75–96.
  32. Dulon D, Aran JM, Zajic G, Schacht J: Comparative uptake of gentamicin, netilmicin, and amikacin in the guinea pig cochlea and vestibule. Antimicrob Agents Chemother 1986;30:96–100.
  33. Dulon D, Aurousseau C, Erre JP, Aran JM: Relationship between the nephrotoxicity and ototoxicity induced by gentamicin in the guinea pig. Acta Otolaryngol 1988;106:219–225.
    External Resources
  34. Dulon D, Zajic G, Aran J-M, Schacht J: Aminoglycoside antibiotics impair calcium-entry but not viability and motility of cochlear outer hair cells. J Neurosci Res 1989;24:338–346.
  35. Edson RS, Terrell CL: The aminoglycosides. Mayo Clin Proc 1999;74:519–528.
    External Resources
  36. Edwards J: Species Differences in Susceptibility to Aminoglycoside Ototoxicity; MSc thesis University College London, 1997.
  37. Ernfors P, Duan ML, El Shamy WM, Canlon B: Protection of auditory neurons from aminoglycoside toxicity by neurotrophin-3. Nat Med 1996;2:463–467.
  38. Fausti SA, Rappaport BZ, Schechter MA, Frey RH, War TT, Brummett RE: Detection of aminoglycoside ototoxicity by high freqency auditory evaluation: Selected case studies. Am J Otolaryngol 1984;5:177–182.
    External Resources
  39. Fee WE: Aminoglycoside ototoxicity in the human. Laryngoscope 1980;40:1–19.
  40. Forge A: Outer hair cell loss and supporting cell expansion following chronic gentamicin treatment. Hear Res 1985;19:171–182.
  41. Forge A, Fradis M: Structural abnormalities in the stria vascularis following chronic gentamicin treatment. Hear Res 1985;20:233–244.
  42. Forge A, Li L: Apoptotic death of hair cells in the mammalian vestibular sensory epithelia. Hear Res 2000;139:97–115.
  43. Forge A, Li L, Corwin JT, Nevill G: Ultrastructural evidence for hair cell regeneration in the mammalian inner ear. Science 1993;259:1616–1619.
  44. Forge A, Li L, Nevill G: Hair cell recovery in the vestibular sensory epithelia of mature guinea pigs. J Comp Neurol 1998;397:69–88.
  45. Forge A, Richardson G: Freeze-fracture analysis of apical membranes in cochlear cultures: Differences between basal and apical-coil outer hair cells and effects of neomycin. J Neurocytol 1993;22:854–867.
  46. Forge A, Wright A, Davies SJ: Analysis of structural changes in the stria vascularis following chronic gentamicin treatment. Hear Res 1987;31:253–266.
  47. Gao WQ: Therapeutic potential of neurotrophins for treatment of hearing loss. Mol Neurobiol 1998;17:17–31.
    External Resources
  48. Garetz SL, Altschuler RA, Schacht J: Attenuation of gentamicin ototoxicity by glutathione in the guinea pig in vivo. Hear Res 1994a;77:81–87.
  49. Garetz SL, Rhee DJ, Schacht J: Sulfhydryl compounds and antioxidants inhibit cytotoxicity to outer hair cells of a gentamicin metabolite in vitro. Hear Res 1994b;77:75–80.
  50. Garetz SL, Schacht J: Ototoxicity: Of mice and men; in Van De Water TR, Fay RR, Popper AN (eds): Clinical Aspects of Hearing. Handbook of Auditory Research. New York, Springer, 1996, vol VII, pp 116–154.
  51. Gitter AH, Oliver D, Thurm U: Streptomycin inhibits discharge in Hydra vulgaris by blockage of mechanosensitivity. Naturwissenschaften 1993;80:273–276.
  52. Hashino E, Shero M, Salvi RJ: Lysosomal targetting and accumulation of aminoglycoside antibiotics in sensory hair cells. Brain Res 1997;777:75–85.
    External Resources
  53. Hashino E, Tanaka Y, Sokabe: Hair cell damage and recovery following chronic application of kanamycin in the chick cochlea. Hear Res 1991;52:356–368.
  54. Hawkins JE: Cochlear signs of streptomycin intoxication. J Pharmacol Exp Ther 1950;100:38–44.
  55. Hawkins JE: Ototoxic mechanisms: A working hypothesis. Audiology 1973;12:383–393.
  56. Hawkins JE: Drug ototoxicity; in Keidel WD, Neff WD (eds): Handbook of Sensory Physiology. Berlin, Springer, 1976, vol 5, part 3, pp 707–748.
  57. Hawkins JE, Beger V, Aran J-M: Antibiotic insults to Corti’s organ; in Graham AB (ed): Sensorineural Hearing Processes and Disorders. Boston, Little Brown, 1967, pp 411–425.
  58. Hawkins JE, Johnsson L-G: Histopathology of cochlear and vestibular ototoxicity in laboratory animals; in Lerner SA, Matz GJ, Hawkins JE Jr (eds): Aminoglycoside Ototoxicity. Boston, Little Brown, 1981, pp 175–195.
  59. Hawkins JE, Stebbins WC, Johnsson L-G, Moody DB, Muraski A: The patas monkey as a model for dihydrostreptomycin ototoxicity. Acta Otolaryngol 1977;83:123–129.
    External Resources
  60. Hayashida T, Hiel H, Dulon D, Erre J-P, Guilhaume A, Aran J-M: Dynamic changes following combined treatment with gentamicin and ethacrynic acid with and without acoustic stimulation: Cellular uptake and functional correlates. Acta Otolaryngol 1989;108:404–413.
    External Resources
  61. Hayashida T, Nomura Y, Iwamori M, Nagai Y, Kurata T: Distribution of gentamicin by immunofluorescence in the guinea pig inner ear. Arch Otorhinolaryngol 1985;242:257–264.
  62. Henley ChM, Gerhardt HJ, Schacht J: Inhibition of inner ear ornithine decarboxylase by neomycin in-vitro. Brain Res Bull 1987;19:695–698.
  63. Henley ChM, Schacht J: Pharmacokinetics of aminoglycoside antibiotics in blood, inner ear fluids and tissues and their relationship to ototoxicity. Audiology 1988;27:137–146.
  64. Hennebert PE: Traitement par le BAL de l’intoxication labyrinthique par la streptomycine. Ann Otolaryngol (Paris) 1951;68:507–508.
  65. Henry KR, Chole RA, McGinn MD, Frush DP: Increased ototoxicity in both young and old mice. Arch Otolaryngol 1981;107:92–95.
    External Resources
  66. Hershko C: Iron chelators in medicine. Mol Aspects Med 1992;13:113–165.
  67. Hiel H, Erre J, Aurousseau C, Bouali R, Dulon D, Aran JM: Gentamicin uptake by cochlear hair cells precedes hearing impairment during chronic treatment. Audiology 1993;32:78–87.
  68. Hiel H, Schamel A, Erre JP, Hayashida T, Dulon D and Aran J-M: Cellular and subcellular localisation of tritiated gentamicin in the guinea pig cochlea following combined treatment with ethacrynic acid. Hearing Res 1992;57:157–165.
  69. Hinojosa R, Lerner SA: Cochlear neural degeneration without hair cell loss in two patients with aminoglycoside ototoxicity. J Infect Dis 1987;156:449–555.
  70. Hinshaw HC, Feldman WH: Streptomycin in treatment of clinical tuberculosis: A preliminary report. Proc Mayo Clin 1945;20:313–318.
  71. Hirose K, Hockenberry DN, Rubel EW: Reactive oxygen species in chick hair cells after gentamicin exposure in vitro. Hear Res 1997;104:1–14.
  72. Hoffman DW, Whitworth CA, Jones-King KL, Rybak LP: Potentiation of ototoxicity by glutathione depletion. Ann Otol Rhinol Laryngol 1988;97:36–41.
  73. Howard M, Frizzell RA, Bedwell DM: Aminoglycoside antibiotics restore CFTR function by overcoming premature stop codons. Nat Med 1996;2:467–469.
  74. Huang MY, Schacht J: Formation of a cytotoxic metabolite from gentamicin by liver. Biochem Pharmacol 1990;40:R11–R14.
  75. Hughes RA, O’Leary PD: Neurotrophic factors and the development of drugs to promote motoneuron survival. Clin Exp Pharmacol Physiol 1996;23:965–969.
    External Resources
  76. Janas JD, Cotanche DA, Rubel EW: Avian cochlear hair cell regeneration: Stereological analyses of damage and recovery from a single high dose of gentamicin. Hear Res 1995;92:17–29.
    External Resources
  77. Johnsson LG, Hawkins JE, Kingsley TC, Black FO, Matz GJ: Aminoglycoside-induced cochlear pathology in man. Acta Otolaryngol 1981;S383:1–19.
  78. Kanno H, Yamanobe S, Rybak LP: The ototoxicity of deferoxamine mesylate. Am J Otolaryngol 1995;16:148–152.
    External Resources
  79. Keller H, Krüpe W, Sous H, Mückter H: Versuche zur Toxizitätsminderung basischer Streptomyces-Antibiotika. 3. Mitteilung: Zum Mechanismus der Streptomycin-Vergiftung und ihre Beeinflussbarkeit durch Pantothensäure. Arzneimittel-Forschung 1956;6:379–384.
  80. Knight JA: Diseases related to oxygen-derived free radicals. Ann Clin Lab Sci 1995;25:111–121.
    External Resources
  81. Komune S, Ide M, Nakano T, Morimitsu T: Effects of kanamycin sulfate on cochlear potentials and potassium ion permeability through the cochlear partitions. ORL 1987;49:9–16.
    External Resources
  82. Kossl M, Richardson GP, Russell IJ: Stereocilia bundle stiffness: Effects of neomycin, A23187 and concanavalin A. Hear Res 1990;44:217–230.
  83. Kotecha B, Richardson GP: Ototoxicity in vitro: Effects of neomycin, gentamicin, dihydrostreptomycin, amikacin, spectinomycin, neamine, spermine and poly-L-lysine. Hear Res 1994;73:173–184.
  84. Kroese ABA, van den Bercken J: Effects of ototoxic antibiotics on sensory hair cell functioning. Hear Res 1982;6:183–197.
  85. Kroese ABA, Das A, Hudspeth AJ: Blockage of the transduction channels of hair cells in the bull frog’s sacculus by aminoglycoside antibiotics. Hear Res 1989;37:203–218.
  86. Kuramochi H, Takahashi K, Takita T, Umezawa H: An active intermediate formed in the reaction of bleomycin-Fe(II) complex with oxygen. J Antibiot (Tokyo) 1981;34:576–582.
    External Resources
  87. Lautermann J, McLaren J, Schacht J: Glutathione protection against gentamicin ototoxicity depends on nutritional status. Hear Res 1995;86:15–24.
  88. Leake PA, Hradek GT: Cochlear pathology of long term neomycin induced deafness in cats. Hear Res 1988;33:11–33.
  89. Leonova EV, Raphael Y: Organization of cell junctions and the cytoskeleton in the reticular lamina in normal and ototoxically damaged organ of Corti. Hear Res 1997;113:14–28.
    External Resources
  90. Lerner SA, Schmitt BA, Seligsohn R, Matz GJ: Comparative study of ototoxicity and nephrotoxicity in patients randomly assigned to treatment with amikacin or gentamicin. Am J Med 1986;80:98–104.
  91. Lewin GR, Barde YA: Physiology of the neurotrophins. Annu Rev Neurosci 1996;19:289–317.
  92. Li L, Forge A: Cultured explants of the vestibular sensory epithelia from adult guinea pigs and effects of gentamicin: A model for examination of hair cell loss and epithelial repair mechanisms. Aud Neurosci 1995;1:111–125.
  93. Li L, Forge A, Nevill G: Apoptotic death of hair cells (abstract 445). Assoc Res Otolaryngol 1997;20.
  94. Li L, Nevill G, Forge A: Two modes of hair cell loss from the vestibular sensory epithelia of the guinea pig. J Comp Neurol 1995;355:405–417.
    External Resources
  95. Liberman MC, Dodds LW, Pierce S: Afferent and efferent innervation of the cat cochlea: Quantitative analysis with light and electron microscopy. J Comp Neurol 1990;301:443–460.
    External Resources
  96. Lim D: Effects of noise and ototoxic drugs at the cellular level in the cochlea: A review. Am J Otolaryngol 1986;7:73–99.
    External Resources
  97. Lin WS, Song XZ: Clinical and experimental research on a kidney-tonifying prescription in preventing and treating children’s hearing loss induced by aminoglycoside antibiotic ototoxicity (in Chinese). Chin J Mod Devel Trad Med 1989;9:402–404.
  98. Lindemann HH: Regional differences in sensitivity of the vestibular sensory epithelia to ototoxic antibiotics. Acta Otolaryngol 1969;67:177–189.
    External Resources
  99. Lodhi S, Weiner ND, Mechigian I, Schacht J: Ototoxicity of aminoglycosides correlated with their action on monomolecular films of polyphosphoinositides. Biochem Pharmacol 1980;29:597–601.
  100. Low W, Dazert S, Baird A, Ryan AF: Basic fibroblast growth factor (FGF-2) protects rat cochlear hair cells in organotypical culture from aminoglycoside injury. J Cell Physiol 1996;167:443–450.
  101. Lu YF: Cause of 611 deaf mutes in schools for deaf children in Shanghai. Shanghai Med J 1987;10:159.
  102. Lyght ChE, Hawkins JE: Streptomycin and dihydrostreptomycin in the treatment of tuberculosis: A comparative study. Transactions 12th Conf on Chemother Tuberculosis. Washington, Veterans Administration, 1953, pp 125–133.
  103. Marchionni MA, Grinspan JB, Canoll PD, Mahanthappa NK, Salzer JL, Scherer SS: Neuregulins as potential neuroprotective agents. Ann NY Acad Sci 1997;825:348–365.
  104. Maroney AC, Glicksman MA, Basma AN, Walton KM, Knight E Jr, Murphy CA, Bartlett BA, Finn JP, Angeles T, Matsuda Y, Neff NT, Dionne CA: Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway. J Neurosci 1998;18:104–111.
  105. Marot M, Uziel A, Romand R: Ototoxicity of kanamycin in developing rats: Relationship with the onset of the auditory function. Hear Res 1980;2:111–113.
  106. Mathog RH, Klein WJ Jr: Ototoxicity of ethacrynic acid and aminoglycoside antibiotics in uremia. N Engl J Med 1969;280:1223–1224.
    External Resources
  107. Meitles L, Raphael Y: Scar formation in the vestibular sensory epithelium after aminoglycoside toxicity. Hear Res 1994;79:26–38.
  108. Mizuta K, Saito A, Watanabe T, Nagure M, Arakawa K, Shimizu F, Hishino T: Ultrastructural localization of megalin in the cochlear duct. Hear Res 1999;129:83–91.
    External Resources
  109. Moestrup SK, Cui S, Vorum H, Bregengard C, Bjorn SE, Norris K, Gliemann J, Christensen EI: Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs. J Clin Invest 1995;96:1404–1413.
    External Resources
  110. Moore RD, Smith CR, Lietman PS: Risk factors for the development of auditory toxicity in patients receiving aminoglycosides. J Infect Dis 1984;149:23–30.
  111. Mulheran M, Degg C: Comparison of distortion product OAE generation between a patient group requiring frequent gentamicin therapy and control subjects. Br J Audiol 1997;31:5–9.
  112. Mulherin D, Fahy J, Grant W, Keogan M, Kavanagh B, Fitzgerald M: Aminoglycoside induced ototoxicity in patients with cystic fibrosis. Ir J Med Sci 1991;160:173–175.
  113. Nadol JB Jr: Patterns of neural degeneration in the human cochlea and auditory nerve: Implications for cochlear implantation. Otolaryngol Head Neck Surg 1997;117:220–228.
  114. Nakagawa T, Yamane H, Takayama M, Sunami K, Nakai Y: Apoptosis of guinea pig cochlear hair cells following aminoglycoside treatment. Eur Arch Otorhinolaryngol 1998;255:127–131.
  115. Nakajima T, Hishida A, Kato A: Mechanisms for protective effects of free radical scavengers on gentamicin-mediated nephropathy in rats. Am J Physiol 1994;266:F425–F431.
    External Resources
  116. Niwa Y, Miyachi Y: Antioxidant action of natural health products and Chinese herbs. Inflammation 1986;10:79–91.
    External Resources
  117. Ohtsuki K, Ohtani I, Aikawa T, Sato Y, Anzai T, Ouchi J, Saito J: The ototoxicity and the accumulation in the inner ear fluids of the various aminoglycoside antibiotics. Ear Res Jpn 1982;13:85–87.
  118. Oppenheim RW: Related mechanisms of action of growth factors and antioxidants in apoptosis: An overview. Adv Neurol 1997;72:69–78.
  119. Peterson CM, Graziano JH, Grady RW, Jones RL, Markenson A, Lavi U, Canale V, Gray GF, Cerami A, Miller DR: Chelation therapy in β-thalassemia major: A one-year double blind study of 2,3-dihydroxybenzoic acid. Exp Hematol 1979;7:74–80.
    External Resources
  120. Pichler M, Wang Z, Grabner-Weiss C, Reimer D, Hering S, Grabner M, Glossmann H, Striessnig J: Block of P/Q-type calcium channels by therapeutic concentrations of aminoglycoside antibiotics. Biochemistry 1996;35:14659–14664.
    External Resources
  121. Pierson MG, Møller AR: Prophylaxis of kanamycin-induced ototoxicity by a radioprotectant. Hear Res 1981;4:79–87.
  122. Pirvola U, Xing-Qun L, Aarnisalo AA, Saarma M, Walton KM, Ylikoski J: CEP-1347 (KT-7515) attenuates hair cell loss following traumas and promotes survival of cochlear neurons (abstract 895). Assoc Res Otolaryngol 1999;22.
  123. Portmanm NM, Darriyzet HM, Ciste C: Distribution within the cochlea of dihydrostreptomycin injected into the circulation. Arch Otolaryngol 1974;100:473–475.
    External Resources
  124. Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, Arnos KS, Cortopassi GA, Jaber L, Rotter JI: Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genetics 1993;4:289–294.
  125. Prezant TR, Shohat M, Jaber L, Pressman S, Fischel-Ghodsian N: Biochemical characterization of a pedigree with mitochondrially inherited deafness. Am J Med Genet 1992;44:465–472.
  126. Pritsos CA, Sartorelli AC: Generation of reactive oxygen radicals through bioactivation of mitomycin antibiotics. Cancer Res 1986;46:3528–3532.
  127. Priuska EM: The Mechanism of Free Radical Formation by Gentamicin: Implications for Ototoxicity; thesis University of Michigan, 1997.
  128. Priuska EM, Clark K, Pecoraro V, Schacht J: NMR spectra of iron-gentamicin complexes and the implications for aminoglycoside toxicity. Inorg Chim Acta 1998;273:85–91.
  129. Priuska EM, Schacht J: Formation of free radicals by gentamicin and iron and evidence for an iron/gentamicin complex. Biochem Pharmacol 1995;50:1749–1752.
    External Resources
  130. Prosen CA, Petersen MR, Moody DB, Stebbins WC: Auditory thresholds and kanamycin-induced hearing loss in the guinea pig assessed by positive reinforcement procedures. J Acoust Soc Am 1978;63:559–566.
    External Resources
  131. Puel JL, Pujol R, Tribillac F, Ladrech S, Eybalin M: Excitatory amino acid antagonists protect cochlear auditory neurons from excitotoxicity. J Comp Neurol 1994;341:241–256.
  132. Pujol R: Periods of sensitivity to antibiotic treatment. Acta Otolaryngol Suppl (Stockh) 1986;429:29–33.
  133. Ramsammy LS, Josepovitz C, Ling K-Y, Lane BP, Kaloyanides GJ: Failure of inhibition of lipid peroxidation by vitamin E to protect against gentamicin nephrotoxicity in the rat. Biochem Pharmacol 1987;36:2125–2132.
  134. Ramsden RT, Wilson P, Gibson WP: Immediate effects of intravenous tobramycin and gentamicin on human cochlear function. J Laryngol Otol 1980;94:521–531.
    External Resources
  135. Ramsey BW, Pepe MS, Quan JM, Otto KL, Montgomery AB, Williams-Warren J, Vasiljev-KM, Borowitz D, Bowman CM, Marshall BC, Marshall S, Smith AL: Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999;340:23–30.
  136. Raphael Y, Altschuler RA: Scar formation after drug-induced cochlear insult. Hear Res 1991;51:173–184.
  137. Raphael Y, Fein A, Nebel L: Transplacental kanamycin ototoxicity in the guinea pig. Arch Otorhinolaryngol 1983;238:45–51.
    External Resources
  138. Raphael Y, Yagi M: Gene transfer and the inner ear. Curr Opin Otolaryngol Head Neck Surg 1998;6:311–315.
  139. Rasmussen F: The ototoxic effect of streptomycin and dihydrostreptomycin on the foetus. Scand J Resp Dis 1969;50:61–67.
    External Resources
  140. Richardson GP, Forge A, Kros CJ, Fleming J, Brown SDM, Steel KP: Myosin VIIA is required for aminoglycoside accumulation in cochlear hair cells. J Neurosci 1997;17:9506–9519.
  141. Richardson GP, Russell IJ: Cochlear culture as a model system for studying aminoglycoside-induced ototoxicity. Hear Res 1991;53:293–311.
  142. Rüedi L, Furrer W, Graf K, Nager G, Tschirren B, Luthy F: Nouvelles constatations sur la toxicité de la streptomycine et de la quinine à l’égard de l’oreille du cobaye. Rev Laryngol (Bord) 1951;72:238–264.
  143. Rüedi L, Furrer W, Luthy F, Nager G, Tschirren B: Further observations concerning the toxic effects of streptomycin and quinine on the auditory organ of guinea pigs. Laryngoscope 1952;62:333–357.
  144. Sande MA, Mandell GL: Antimicrobial agents: The aminoglycosides; in Gilman AG, Rall TW, Nies AS, Taylor P (eds): The Pharmacological Basis of Therapeutics. New York, Pergamon Press, 1990, p 1102.
  145. Satoh T, Enokido Y, Kubo T, Yamada M, Hatanaka H: Oxygen toxicity induces apoptosis in neuronal cells. Cell Mol Neurobiol 1998;18:649–666.
    External Resources
  146. Schacht J: Isolation of an aminoglycoside receptor from guinea pig inner ear tissues and kidney. Arch Otorhinolaryngol 1979;224:129–134.
    External Resources
  147. Schatz A, Bugie E, Waksman SA: Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc Soc Exp Biol Med 1944;55:66–69.
  148. Shah SB, Gladstone HB, Williams H, Hradek GT, Schindler RA: An extended study: Protective effects of nerve growth factor in neomycin-induced auditory neural degeneration. Am J Otol 1995;16:310–314.
  149. Sha S-H, Schacht J: Are aminoglycoside antibiotics excitotoxic? Neuroreport 1998;9:3893–3895.
  150. Sha S-H, Schacht J: Formation of free radicals by aminoglycoside antibiotics. Hear Res 1999a;128:112–118.
  151. Sha S-H, Schacht J: Formation of reactive oxygen species following bioactivation of gentamicin. Free Radical Biol Med 1999b;26:341–347.
  152. Sha S-H, Schacht J: Salicylate attenuates gentamicin-induced ototoxicity. Lab Invest 1999c;79:807–813.
  153. Sha S-H, Taylor R, Forge A, Schacht J: Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals (abstract 150). Assoc Res Otolaryngol 2000;23.
  154. Sha S-H, Zajic G, Schacht J: Transgenic mice overexpressing copper-zinc superoxide dismutase are protected from kanamycin-induced ototoxicity (abstract 122). Assoc Res Otolaryngol 1997;20.
  155. Shafer RW, Goldberg R, Sierra M, Glatt AE: Frequency of Mycobacterium tuberculosis bacteremia in patients with tuberculosis in an area endemic for AIDS. Am Rev Respir Dis 1989;140:1611–1613.
    External Resources
  156. She W-D, Chen Z-H: Experimental study of antioxidation of ligustrazine on kanamycin ototoxicity. Proc Sendai Symp 1995;5:59–61.
  157. Sone M, Schachern PA, Paparella MM: Loss of spiral ganglion cells as primary manifestation of aminoglycoside ototoxicity. Hear Res 1998;115:217–223.
  158. Song B-B, Anderson DJ, Schacht J: Protection from gentamicin ototoxicity by iron chelators in guinea pig in vivo. J Pharmacol Exp Ther 1997;282:369–377.
  159. Song B-B, Schacht J: Variable efficacy of radical scavengers and iron chelators to attenuate gentamicin ototoxicity in guinea pig in vivo. Hear Res 1996;94:87–93.
  160. Song B-B, Sha S-H, Schacht J: Iron chelators protect from aminoglycoside-induced cochleo- and vestibulotoxicity in guinea pig. Free Radic Biol Med 1998;25:189–195.
  161. Stebbins WC, McGinn CS, Feitosa MAG, Moody DB, Prosen CA, Serafin JV: Animal models in the study of ototoxic hearing loss; in Lerner SA, Matz GJ, Hawkins JE (eds): Aminoglycoside Ototoxicity. Boston, Little Brown, 1981, pp 5–25.
  162. Stebbins WC, Miller JM, Johnsson L-G, Hawkins JE: Ototoxic hearing loss and cochlear pathology in the monkey. Ann Otol 1969;78:1007–1025.
    External Resources
  163. Stratta P, Segoloni GP, Canavese C, Muzio G, Dogliani M, Serra A, Allemandi P, Salomone M, Caramellino C, Canuto R: Oxygen free radicals are not the main factor in experimental gentamicin nephrotoxicity. Ren Fail 1994;16:445–455.
    External Resources
  164. Swan SK: Aminoglycoside nephrotoxicity. Semin Nephrol 1997;17:27–33.
    External Resources
  165. Takada A, Schacht J: Calcium antagonism and reversibility of gentamicin-induced loss of cochlear microphonics in the guinea pig. Hear Res 1982;8:179–186.
  166. Tan S, Sagara Y, Liu Y, Maher P, Schubert D: The regulation of reactive oxygen species production during programmed cell death. J Cell Biol 1998;141:1423–1432.
  167. Tanswell AK, Freeman BA: Antioxidant therapy in critical care medicine. New Horiz 1995;3:330–341.
    External Resources
  168. Tong L, Toliver-Kinsky T, Taglialatela G, Werrbach-Perez K, Wood T, Perez-Polo R: Signal transduction in neuronal death. J Neurochem 1998;71:447–459.
    External Resources
  169. Tran Ba Huy P, Bernard P, Schacht J: Kinetics of gentamicin uptake and release in the rat: Comparison of inner ear tissues and fluids with other organs. J Clin Invest 1986;77:1492–1500.
  170. Usami S, Abe S, Tono T, Komune S, Kimberling WJ, Shinkawa H: Isepamicin sulfate-induced sensorineural hearing loss in patients with the 1555 A→G mitochondrial mutation. ORL 1998;60:164–169.
  171. Usami S, Hjelle OP, Ottersen OP: Differential cellular distribution of glutathione – an endogenous antioxidant – in the guinea pig inner ear. Brain Res 1996;743:337–340.
  172. Vital-Brazil O, Corrado AP: The curariform action of streptomycin. J Pharmacol Exp Ther 1957;120:452–459.
  173. Von Ilberg C, Spoendlin H, Arnold W: Autoradiographical distribution of locally applied dihydrostreptomycin in the inner ear. Acta Otolaryngol 1971;71:159–165.
    External Resources
  174. Walker PD, Shah SV: Gentamicin enhanced production of hydrogen peroxide by renal cortical mitochondria. Am J Physiol 1987;253:C495–C499.
    External Resources
  175. Walker PD, Shah SV: Evidence suggesting a role for hydroxyl radical in gentamicin-induced acute renal failure in rats. J Clin Invest 1988;81:334–341.
    External Resources
  176. Wang BM, Weiner ND, Takada A, Schacht J: Characterization of aminoglycoside-lipid interactions and development of a refined model for ototoxicity testing. Biochem Pharmacol 1984;33:3257–3262.
  177. Webster M, Webster DB: Spiral ganglion neuron loss following organ of Corti loss: A quantitative study. Brain Res 1981;212:17–30.
  178. Wersäll J, Björkroth B, Flock A, Lundquist P-G: Experiments on ototoxic effects of antibiotics. Adv Otorhinolaryngol 1973;20:14–41.
    External Resources
  179. Wersäll J, Flock Å: Suppression and restoration of the microphonic output from the lateral line organ after local application of streptomycin. Life Sci 1964;3:1151–1155.
    External Resources
  180. Wersäll J, Lundquist P-G, Björkroth B: Ototoxicity of gentamicin. J Infect Dis 1969;119:410–416.
  181. West BA, Brummet RE, Himes DL: Interaction of kanamycin and ethacrynic acid. Arch Otolaryngol 1973;98:32–37.
    External Resources
  182. Williams SE, Smith DE, Schacht J: Characteristics of gentamicin uptake in the isolated crista ampullaris of the inner ear of the guinea pig. Biochem Pharmacol 1987;36:89–95.
  183. Wong CH, Hendrix M, Priestley ES, Greenberg WA: Specificity of aminoglycoside antibiotics for the A-site of the decoding region of ribosomal RNA. Chem Biol 1998;5:397–406.
    External Resources
  184. Wright T: Ototoxicity; in Ludman H, Wright T (eds): Diseases of the Ear, ed 6. London, Arnold, 1998, pp 502–515.
  185. Xuan W, Dong M, Dong M: Effects of compound injection of Pyrola rotundifolia L and Astragalus membranaceus Bge on experimental guinea pigs’ gentamicin ototoxicity. Ann Otol Rhinol Laryngol 1995;104:374–380.
  186. Yagi M, Magal E, Sheng Z, Ang KA, Raphael Y: Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor. Hum Gene Ther 1999;10:813–823.
  187. Yang CL, Du XH, Han YX: Renal cortical mitochondria are the source of oxygen free radicals enhanced by gentamicin. Ren Fail 1995;17:21–26.
    External Resources
  188. Yin MJ, Yamamoto Y, Gaynor RB: The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 1998;396:77–80.
  189. Ylikoski J, Pirvola U, Zhai S, Eriksson U, Solin M, Miettinen A: Aminoglycoside ototoxicity: High affinity receptors are expressed in secretory epithelia. Aud Neurosci 1997;3:415–424.
  190. Zajic G, Schacht J: Immunocytochemical localization of megalin and alpha-2-macroglobulin within guinea pig cochlear tissues. Abstr Assoc Res Otolaryngol 1997;20:158.
  191. Zappia JJ, Altschuler RA: Evaluation of the effect of ototopical neomycin on spiral ganglion cell density in the guinea pig. Hear Res 1989;40:29–38.
  192. Zheng JL, Gao WQ: Differential damage to auditory neurons and hair cells by ototoxins and neuroprotection by specific neurotrophins in rat cochlear organotypic cultures. Eur J Neurosci 1996;8:1897–1905.
  193. Zheng JL, Stewart RR, Gao WQ: Neurotrophin-4/5, brain-derived neurotrophic factor, and neurotrophin-3 promote survival of cultured vestibular ganglion neurons and protect them against neurotoxicity of ototoxins. J Neurobiol 1995;28:330–440.

Article / Publication Details

First-Page Preview
Abstract of Review

Published online: February 10, 2000
Issue release date: January – February

Number of Print Pages: 20
Number of Figures: 4
Number of Tables: 2

ISSN: 1420-3030 (Print)
eISSN: 1421-9700 (Online)

For additional information: https://www.karger.com/AUD


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.