Table of Contents Author Guidelines Submit a Manuscript
International Journal of Otolaryngology
Volume 2011, Article ID 937861, 19 pages
http://dx.doi.org/10.1155/2011/937861
Review Article

Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection

1Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA 94305-5739, USA
2Department of Otorhinolaryngology, Head and Neck Surgery, Inselspital, University of Bern, Freiburgstrasse, 3010 Bern, Switzerland
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA

Received 2 June 2011; Accepted 18 August 2011

Academic Editor: Jeffrey P. Pearson

Copyright © 2011 M. E. Huth et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Schatz, E. Bugie, and S. A. Waksman, “Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria,” Proceedings of the Society for Experimental Biology and Medicine, vol. 55, pp. 66–69, 1944. View at Google Scholar
  2. S. Waksman, “Streptomycin: background, isolation, properties, and utilization,” Nobel prize lecture, Nobel Organization, 1952, http://nobelprize.org/nobel_prizes/medicine/laureates/1952/waksman-lecture.pdf.
  3. H. Umezawa et al., “Production and isolation of a new antibiotic: kanamycin,” The Journal of Antibiotics, vol. 10, no. 5, pp. 181–188, 1957. View at Google Scholar · View at Scopus
  4. S. A. Waksman and H. A. Lechevalier, “Neomycin, a new antibiotic active against streptomycin-resistant bacteria, including tuberculosis organisms,” Science, vol. 109, no. 2830, pp. 305–307, 1949. View at Google Scholar · View at Scopus
  5. M. J. Weinstein, G. M. Luedemann, E. M. Oden et al., “Gentamicin, a new antibiotic complex from Micromonospora,” Journal of Medicinal Chemistry, vol. 6, no. 4, pp. 463–464, 1963. View at Google Scholar · View at Scopus
  6. H. Kawaguchi, “Discovery, chemistry, and activity of amikacin,” Journal of Infectious Diseases, vol. 134, supplement, pp. S242–S248, 1976. View at Google Scholar
  7. R. H. Drew, “Aminoglycosides,” 2011, http://www.uptodate.com.
  8. R. Hock and R. J. Anderson, “Prevention of drug-induced nephrotoxicity in the intensive care unit,” Journal of Critical Care, vol. 10, no. 1, pp. 33–43, 1995. View at Google Scholar · View at Scopus
  9. G. Toubeau, G. Laurent, and M. B. Carlier, “Tissue repair in rat kidney cortex after short treatment with aminoglycosides at low doses. A comparative biochemical and morphometric study,” Laboratory Investigation, vol. 54, no. 4, pp. 385–393, 1986. View at Google Scholar · View at Scopus
  10. G. J. Greenwood, “Neomycin ototoxicity; report of a case,” A.M.A. Archives of Otolaryngology, vol. 69, no. 4, pp. 390–397, 1959. View at Google Scholar
  11. R. A. Hettig and J. D. Adcock, “Studies on the toxicity of streptomycin for man: a preliminary report,” Science, vol. 103, no. 2673, pp. 355–357, 1946. View at Google Scholar · View at Scopus
  12. H. C. Hinshaw, W. H. Feldman, and K. H. Pfuetze, “Treatment of tuberculosis with streptomycin; a summary of observations on one hundred cases,” Journal of the American Medical Association, vol. 132, no. 13, pp. 778–782, 1946. View at Google Scholar
  13. G. Matz, L. Rybak, P. S. Roland et al., “Ototoxicity of ototopical antibiotic drops in humans,” Otolaryngology—Head and Neck Surgery, vol. 130, no. 3, pp. S79–S82, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. M. D. Rizzi and K. Hirose, “Aminoglycoside ototoxicity,” Current Opinion in Otolaryngology and Head and Neck Surgery, vol. 15, no. 5, pp. 352–357, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. G. J. Matz, “Aminoglycoside cochlear ototoxicity,” Otolaryngologic Clinics of North America, vol. 26, no. 5, pp. 705–712, 1993. View at Google Scholar · View at Scopus
  16. W. E. Heck, H. C. Hinshaw, and H. G. Parsons, “Auditory ototoxicity in tuberculosis patients treated with a report of the incidence of hearing loss in a series of 1,150 cases,” Journal of the American Medical Association, vol. 86, pp. 18–20, 1963. View at Google Scholar
  17. W. E. Fee, “Aminoglycoside ototoxicity in the human,” Laryngoscope, vol. 90, no. 10, pp. 1–19, 1980. View at Google Scholar · View at Scopus
  18. M. Mulheran, C. Degg, S. Burr, D. W. Morgan, and D. E. Stableforth, “Occurrence and risk of cochleotoxicity in cystic fibrosis patients receiving repeated high-dose aminoglycoside therapy,” Antimicrobial Agents and Chemotherapy, vol. 45, no. 9, pp. 2502–2509, 2001. View at Publisher · View at Google Scholar · View at Scopus
  19. L. P. Rybak and J. Schacht, “Drug-induced hearing loss,” in Auditory Trauma, Protection and Repair, P. A. Schacht and R. R. Fay, Eds., pp. 219–256, Springer, New York, NY, USA, 2008. View at Google Scholar
  20. J. M. Aran and J. Darrouzet, “Observation of click evoked compound VIII nerve responses before, during, and over seven months after kanamycin treatment in the guinea pig,” Acta Oto-Laryngologica, vol. 79, no. 1-2, pp. 24–32, 1975. View at Google Scholar · View at Scopus
  21. J. E. Hawkins and L.G. Johnson, “Histopathology of cochlear and vestibular ototoxicity in laboratory animals,” in Aminoglycoside Ototoxicity, S. A. Lerner, G. J. Matz, and J. E. Hawkins, Eds., pp. 327–339, Little & Brown, Boston, Mass, USA, 1981. View at Google Scholar
  22. S. A. Fausti, J. A. Henry, H. I. Schaffer, D. J. Olson, R. H. Frey, and W. J. McDonald, “High-frequency audiometric monitoring for early detection of aminoglycoside ototoxicity,” Journal of Infectious Diseases, vol. 165, no. 6, pp. 1026–1032, 1992. View at Google Scholar · View at Scopus
  23. L. A. Grohskopf, W. C. Huskins, R. L. Sinkowitz-Cochran, G. L. Levine, D. A. Goldmann, and W. R. Jarvis, “Use of antimicrobial agents in United States neonatal and pediatric intensive care patients,” Pediatric Infectious Disease Journal, vol. 24, no. 9, pp. 766–773, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. K. E. Price, “Aminoglycoside research 1975–1985: prospects for development of improved agents,” Antimicrobial Agents and Chemotherapy, vol. 29, no. 4, pp. 543–548, 1986. View at Google Scholar · View at Scopus
  25. E. Durante-Mangoni, A. Grammatikos, R. Utili, and M. E. Falagas, “Do we still need the aminoglycosides?” International Journal of Antimicrobial Agents, vol. 33, no. 3, pp. 201–205, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. J. A. Caminero, G. Sotgiu, A. Zumla, and G. B. Migliori, “Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis,” The Lancet Infectious Diseases, vol. 10, no. 9, pp. 621–629, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. G. M. Pacifici, “Clinical pharmacokinetics of aminoglycosides in the neonate: a review,” European Journal of Clinical Pharmacology, vol. 65, no. 4, pp. 419–427, 2009. View at Publisher · View at Google Scholar · View at Scopus
  28. J. Schacht, “Biochemical basis of aminoglycoside ototoxicity,” Otolaryngologic Clinics of North America, vol. 26, no. 5, pp. 845–856, 1993. View at Google Scholar · View at Scopus
  29. P. J. L. Daniels, A. K. Mallams, J. Weinstein, J. J. Wright, and G. W. A. Milne, “Mass spectral studies on aminocyclitol-aminoglycoside antibiotics,” Journal of the Chemical Society, Perkin Transactions 1, no. 10, pp. 1078–1088, 1976. View at Google Scholar · View at Scopus
  30. P. D. Damper and W. Epstein, “Role of the membrane potential in bacterial resistance to aminoglycoside antibiotics,” Antimicrobial Agents and Chemotherapy, vol. 20, no. 6, pp. 803–808, 1981. View at Google Scholar · View at Scopus
  31. S. Jana and J. K. Deb, “Molecular understanding of aminoglycoside action and resistance,” Applied Microbiology and Biotechnology, vol. 70, no. 2, pp. 140–150, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. J. G. Silva and I. Carvalho, “New insights into aminoglycoside antibiotics and derivatives,” Current Medicinal Chemistry, vol. 14, no. 10, pp. 1101–1119, 2007. View at Publisher · View at Google Scholar · View at Scopus
  33. R. Garraffo, H. B. Drugeon, P. Dellamonica, E. Bernard, and P. Lapalus, “Determination of optimal dosage regimen for amikacin in healthy volunteers by study of pharmacokinetics and bactericidal activity,” Antimicrobial Agents and Chemotherapy, vol. 34, no. 4, pp. 614–621, 1990. View at Google Scholar · View at Scopus
  34. A. I. Al-Amoud, B. J. Clark, and H. Chrystyn, “Determination of gentamicin in urine samples after inhalation by reversed-phase high-performance liquid chromatography using pre-column derivatisation with o-phthalaldehyde,” Journal of Chromatography B, vol. 769, no. 1, pp. 89–95, 2002. View at Publisher · View at Google Scholar
  35. K. G. Naber, S. R. Westenfelder, and P. O. Madsen, “Pharmacokinetics of the aminoglycoside antibiotic tobramycin in humans,” Antimicrobial Agents and Chemotherapy, vol. 3, no. 4, pp. 469–473, 1973. View at Google Scholar · View at Scopus
  36. J. M. Walker, R. Wise, and M. Mitchard, “The pharmacokinetics of amikacin and gentamicin in volunteers: a comparison of individual differences,” Journal of Antimicrobial Chemotherapy, vol. 5, no. 1, pp. 95–99, 1979. View at Google Scholar · View at Scopus
  37. D. S. Hoff, R. A. Wilcox, L. M. Tollefson, P. G. Lipnik, A. R. Commers, and M. Liu, “Pharmacokinetic outcomes of a simplified, weight-based, extended-interval gentamicin dosing protocol in critically ill neonates,” Pharmacotherapy, vol. 29, no. 11, pp. 1297–1305, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. C. R. Kumana and K. H. Yuen, “Parenteral aminoglycoside therapy: selection, administration and monitoring,” Drugs, vol. 47, no. 6, pp. 902–913, 1994. View at Google Scholar · View at Scopus
  39. L. D. Sabath and I. Toftegaard, “Rapid microassays for clindamycin and gentamicin when present together and the effect of pH and of each on the antibacterial activity of the other,” Antimicrobial agents and chemotherapy, vol. 6, no. 1, pp. 54–59, 1974. View at Google Scholar · View at Scopus
  40. A. Hinz et al., “Membrane proteases and aminoglycoside antibiotic resistance,” The Journal of Bacteriology, vol. 139, no. 18, pp. 4790–4797, 2011. View at Google Scholar
  41. E. P. Abraham and E. S. Duthie, “Effect of pH of the medium on activity of streptomycin and penicillin and other chemotherapeutic substances,” The Lancet, vol. 247, no. 6396, pp. 455–459, 1946. View at Google Scholar · View at Scopus
  42. R. E. W. Hancock, S. W. Farmer, Z. Li, and K. Poole, “Interaction of aminoglycosides with the outer membranes and purified lipopolysaccharide and OmpF porin of Escherichia coli,” Antimicrobial Agents and Chemotherapy, vol. 35, no. 7, pp. 1309–1314, 1991. View at Google Scholar · View at Scopus
  43. A. A. Peterson, R. E. W. Hancock, and E. J. McGroarty, “Binding of polycationic antibiotics and polyamines to lipopolysaccharides of Pseudomonas aeruginosa,” Journal of Bacteriology, vol. 164, no. 3, pp. 1256–1261, 1985. View at Google Scholar · View at Scopus
  44. P. R. G. Schindler and M. Teuber, “Action of polymyxin B on bacterial membranes: morphological changes in the cytoplasm and in the outer membrane of Salmonella typhimurium and Escherichia coli B,” Antimicrobial Agents and Chemotherapy, vol. 8, no. 1, pp. 95–104, 1975. View at Google Scholar · View at Scopus
  45. N. L. Martin and T. J. Beveridge, “Gentamicin interaction with Pseudomonas aeruginosa cell envelope,” Antimicrobial Agents and Chemotherapy, vol. 29, no. 6, pp. 1079–1087, 1986. View at Google Scholar · View at Scopus
  46. J. L. Kadurugamuwa, J. S. Lam, and T. J. Beveridge, “Interaction of gentamicin with the A band and B band lipopolysaccharides of Pseudomonas aeruginosa and its possible lethal effect,” Antimicrobial Agents and Chemotherapy, vol. 37, no. 4, pp. 715–721, 1993. View at Google Scholar · View at Scopus
  47. L. E. Bryan and H. M. Van Den Elzen, “Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria,” Antimicrobial Agents and Chemotherapy, vol. 12, no. 2, pp. 163–177, 1977. View at Google Scholar · View at Scopus
  48. E. C. Cox, J. R. White, and J. G. Flaks, “Streptomycin action and the ribosome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 51, pp. 703–709, 1964. View at Google Scholar
  49. J. Davies, P. Anderson, and B. D. Davis, “Inhibition of protein synthesis by spectinomycin,” Science, vol. 149, no. 3688, pp. 1096–1098, 1965. View at Google Scholar · View at Scopus
  50. L. E. Bryan and S. Kwan, “Roles of ribosomal binding, membrane potential, and electron transport in bacterial upake of streptomycin and gentamicin,” Antimicrobial Agents and Chemotherapy, vol. 23, no. 6, pp. 835–845, 1983. View at Google Scholar
  51. R. Green and H. F. Noller, “Ribosomes and translation,” Annual Review of Biochemistry, vol. 66, pp. 679–716, 1997. View at Publisher · View at Google Scholar · View at Scopus
  52. R. T. Garvin, D. K. Biswas, and L. Gorini, “The effects of streptomycin or dihydrostreptomycin binding to 16S RNA or to 30S ribosomal subunits,” Proceedings of the National Academy of Sciences of the United States of America, vol. 71, no. 10, pp. 3814–3818, 1974. View at Google Scholar · View at Scopus
  53. J. Davies and B. D. Davis, “Misreading of ribonucleic acid code words induced by aminoglycoside antibiotics. The effect of drug concentration,” Journal of Biological Chemistry, vol. 243, no. 12, pp. 3312–3316, 1968. View at Google Scholar · View at Scopus
  54. M. J. Cabanas, D. Vazquez, and J. Modolell, “Inhibition of ribosomal translocation by aminoglycoside antibiotics,” Biochemical and Biophysical Research Communications, vol. 83, no. 3, pp. 991–997, 1978. View at Google Scholar · View at Scopus
  55. M. Misumi, T. Nishimura, T. Komai, and N. Tanaka, “Interaction of kanamycin and related antibiotics with the large subunit of ribosomes and the inhibition of translocation,” Biochemical and Biophysical Research Communications, vol. 84, no. 2, pp. 358–365, 1978. View at Google Scholar · View at Scopus
  56. K. Fredrick and H. F. Noller, “Catalysis of ribosomal translocation by sparsomycin,” Science, vol. 300, no. 5622, pp. 1159–1162, 2003. View at Publisher · View at Google Scholar · View at Scopus
  57. M. B. Feldman, D. S. Terry, R. B. Altman, and S. C. Blanchard, “Aminoglycoside activity observed on single pre-translocation ribosome complexes.,” Nature Chemical Biology, vol. 6, no. 1, pp. 54–62, 2010. View at Google Scholar · View at Scopus
  58. D. Fourmy, M. I. Recht, and J. D. Puglisi, “Binding of neomycin-class aminoglycoside antibiotics to the A-site of 16 S rRNA,” Journal of Molecular Biology, vol. 277, no. 2, pp. 347–362, 1998. View at Publisher · View at Google Scholar · View at Scopus
  59. H. F. Noller, “Ribosomal RNA and translation,” Annual Review of Biochemistry, vol. 60, pp. 191–227, 1991. View at Google Scholar · View at Scopus
  60. A. R. Smyth and J. Bhatt, “Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis,” Cochrane database of systematic reviews (Online), vol. 1, article CD002009, 2010. View at Google Scholar · View at Scopus
  61. N. Fischel-Ghodsian, “Genetic factors in aminoglycoside toxicity,” Pharmacogenomics, vol. 6, no. 1, pp. 27–36, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. D. N. Hu, W. Q. Qiu, B. T. Wu et al., “Genetic aspects of antibiotic induced deafness: mitochondrial inheritance,” Journal of Medical Genetics, vol. 28, no. 2, pp. 79–83, 1991. View at Google Scholar · View at Scopus
  63. T. Hutchin, I. Haworth, K. Higashi et al., “A molecular basis for human hypersensitivity to aminoglycoside antibiotics,” Nucleic Acids Research, vol. 21, no. 18, pp. 4174–4179, 1993. View at Google Scholar · View at Scopus
  64. E. Ruiz-Pesini and D. C. Wallace, “Evidence for adaptive selection acting on the tRNA and rRNA genes of human mitochondrial DNA,” Human Mutation, vol. 27, no. 11, pp. 1072–1081, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. T. R. Prezant, J. V. Agapian, M. C. Bohlman et al., “Mitochondrial ribosomal RNA mutation associated with both antibiotic- induced and non-syndromic deafness,” Nature Genetics, vol. 4, no. 3, pp. 289–294, 1993. View at Publisher · View at Google Scholar · View at Scopus
  66. H. Zhao, R. Li, Q. Wang et al., “Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNa gene in a large Chinese family,” American Journal of Human Genetics, vol. 74, no. 1, pp. 139–152, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Li and A. Tzagoloff, “Identification of the paromomycin-resistance mutation in the 15 S rRNA gene of yeast mitochondria,” Journal of Biological Chemistry, vol. 257, no. 10, pp. 5921–5928, 1982. View at Google Scholar · View at Scopus
  68. E. A. Spangler and E. H. Blackburn, “The nucleotide sequence of the 17 S ribosomal RNA gene of Tetrahymena thermophila and the identification of point mutations resulting in resistance to the antibiotics paromomycin and hygromycin,” Journal of Biological Chemistry, vol. 260, no. 10, pp. 6334–6340, 1985. View at Google Scholar · View at Scopus
  69. S. N. Hobbie, S. Akshay, S. K. Kalapala, C. M. Bruell, D. Shcherbakov, and E. C. Böttger, “Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 52, pp. 20888–20893, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. K. Hamasaki and R. R. Rando, “Specific binding of aminoglycosides to a human rRNA construct based on a DNA polymorphism which causes aminoglycoside-induced deafness,” Biochemistry, vol. 36, no. 40, pp. 12323–12328, 1997. View at Publisher · View at Google Scholar · View at Scopus
  71. G. E. Hyde, “Mitochondrial role in hair cell survival after injury,” Otolaryngology—Head and Neck Surgery, vol. 113, no. 5, pp. 530–540, 1995. View at Publisher · View at Google Scholar · View at Scopus
  72. K. N. Owens, D. E. Cunningham, G. Macdonald, E. W. Rubel, D. W. Raible, and R. Pujol, “Ultrastructural analysis of aminoglycoside-induced hair cell death in the zebrafish lateral line reveals an early mitochondrial response,” Journal of Comparative Neurology, vol. 502, no. 4, pp. 522–543, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. M. L. Avent et al., “Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity,” Internal Medicine Journal, vol. 41, no. 6, pp. 441–449, 2011. View at Publisher · View at Google Scholar
  74. M. Bitner-Glindzicz, M. Pembrey, A. Duncan et al., “Prevalence of mitochondrial 1555A→G mutation in European children,” The New England Journal of Medicine, vol. 360, no. 6, pp. 640–642, 2009. View at Google Scholar · View at Scopus
  75. J. Chen, L. Yang, A. Yang et al., “Maternally inherited aminoglycoside-induced and nonsyndromic hearing loss is associated with the 12S rRNA C1494T mutation in three Han Chinese pedigrees,” Gene, vol. 401, no. 1-2, pp. 4–11, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Ealy, K. A. Lynch, N. C. Meyer, and R. J.H. Smith, “The prevalence of mitochondrial mutations associated with aminoglycoside-induced sensorineural hearing loss in an NICU population,” Laryngoscope, vol. 121, no. 6, pp. 1184–1186, 2011. View at Publisher · View at Google Scholar
  77. Y. Zhu, Q. Li, Z. Chen et al., “Mitochondrial haplotype and phenotype of 13 Chinese families may suggest multi-original evolution of mitochondrial C1494T mutation,” Mitochondrion, vol. 9, no. 6, pp. 418–428, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. R. F. Johnson, A. P. Cohen, Y. Guo, K. Schibler, and J. H. Greinwald, “Genetic mutations and aminoglycoside-induced ototoxicity in neonates,” Otolaryngology—Head and Neck Surgery, vol. 142, no. 5, pp. 704–707, 2010. View at Google Scholar · View at Scopus
  79. N. Fischel-Ghodsian, T. R. Prezant, X. Bu, and S. Oztas, “Mitochondrial ribosomal RNA gene mutation in a patient with sporadic aminoglycoside ototoxicity,” American Journal of Otolaryngology—Head and Neck Medicine and Surgery, vol. 14, no. 6, pp. 399–403, 1993. View at Publisher · View at Google Scholar · View at Scopus
  80. R. A. M. S. Casano, D. F. Johnson, Y. Bykhovskaya, F. Torricelli, M. Bigozzi, and N. Fischel-Ghodsian, “Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications,” American Journal of Otolaryngology—Head and Neck Medicine and Surgery, vol. 20, no. 3, pp. 151–156, 1999. View at Publisher · View at Google Scholar · View at Scopus
  81. T. Tono, K. Kiyomizu, K. Matsuda et al., “Different clinical characteristics of aminoglycoside-induced profound deafness with and without the 1555 A→G mitochondrial mutation,” ORL, vol. 63, no. 1, pp. 25–30, 2001. View at Publisher · View at Google Scholar · View at Scopus
  82. G. Cortopassi and T. Hutchin, “A molecular and cellular hypothesis for aminoglycoside-induced deafness,” Hearing Research, vol. 78, no. 1, pp. 27–30, 1994. View at Publisher · View at Google Scholar · View at Scopus
  83. J. R. Lindsay and R. Hinojosa, “Histopathologic features of the inner ear associated with Kearns Sayre syndrome,” Archives of Otolaryngology, vol. 102, no. 12, pp. 747–752, 1976. View at Google Scholar · View at Scopus
  84. A. Pandya, Nonsyndromic Hearing Loss and Deafness, Mitochondrial, 1993.
  85. G. Al-Malky et al., “Aminoglycoside antibiotics cochleotoxicity in paediatric cystic fibrosis (CF) patients: a study using extended high-frequency audiometry and distortion product otoacoustic emissions,” International Journal of Audiology, vol. 50, no. 2, pp. 112–122, 2011. View at Google Scholar
  86. D. Dulon, J. M. Aran, G. Zajic, and J. Schacht, “Comparative uptake of gentamicin, netilmicin, and amikacin in the guinea pig cochlea and vestibule,” Antimicrobial Agents and Chemotherapy, vol. 30, no. 1, pp. 96–100, 1986. View at Google Scholar · View at Scopus
  87. Q. Wang and P. S. Steyger, “Trafficking of systemic fluorescent gentamicin into the cochlea and hair cells,” Journal of the Association for Research in Otolaryngology, vol. 10, no. 2, pp. 205–219, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. S. Imaimura and J. C. Adams, “Distribution of gentamicin in the guinea pig inner ear after local or systemic application,” Journal of the Association for Research in Otolaryngology, vol. 4, no. 2, pp. 176–195, 2003. View at Publisher · View at Google Scholar
  89. P. Tran Ba Huy, P. Bernard, and J. Schacht, “Kinetics of gentamicin uptake and release in the rat. Comparison of inner ear tissues and fluids with other organs,” Journal of Clinical Investigation, vol. 77, no. 5, pp. 1492–1500, 1986. View at Google Scholar · View at Scopus
  90. E. Hashino and M. Shero, “Endocytosis of aminoglycoside antibiotics in sensory hair cells,” Brain Research, vol. 704, no. 1, pp. 135–140, 1995. View at Publisher · View at Google Scholar · View at Scopus
  91. G. P. Richardson, A. Forge, C. J. Kros, J. Fleming, S. D. M. Brown, and K. P. Steel, “Myosin VIIA is required for aminoglycoside accumulation in cochlear hair cells,” Journal of Neuroscience, vol. 17, no. 24, pp. 9506–9519, 1997. View at Google Scholar · View at Scopus
  92. W. Marcotti, S. M. van Netten, and C. J. Kros, “The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano-electrical transducer channels,” Journal of Physiology, vol. 567, no. 2, pp. 505–521, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. P. S. Steyger, S. L. Peters, J. Rehling, A. Hordichok, and C. F. Dai, “Uptake of gentamicin by bullfrog saccular hair cells in vitro,” Journal of the Association for Research in Otolaryngology, vol. 4, no. 4, pp. 565–578, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. J. R. Waguespack and A. J. Ricci, “Aminoglycoside ototoxicity: permeant drugs cause permanent hair cell loss,” Journal of Physiology, vol. 567, no. 2, pp. 359–360, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. J. Darrouzet and A. Guilhaume, “Ototoxicité de la kanamycine au jour le jour. Étude expérimentale en microscopie électronique,” Revue de Laryngologie Otologie Rhinologie, vol. 95, no. 9-10, pp. 601–621, 1974. View at Google Scholar
  96. T. Hasson, P. G. Gillespie, J. A. Garcia et al., “Unconventional myosins in inner-ear sensory epithelia,” Journal of Cell Biology, vol. 137, no. 6, pp. 1287–1307, 1997. View at Publisher · View at Google Scholar · View at Scopus
  97. C. J. Kros, W. Marcotti, S. M. Van Netten et al., “Reduced climbing and increased slipping adaptation in cochlear hair cells of mice with Myo7a mutations,” Nature Neuroscience, vol. 5, no. 1, pp. 41–47, 2002. View at Publisher · View at Google Scholar · View at Scopus
  98. Z. Mamdouh, M. C. Giocondi, R. Laprade, and C. Le Grimellec, “Temperature dependence of endocytosis in renal epithelial cells in culture,” Biochimica et Biophysica Acta, vol. 1282, no. 2, pp. 171–173, 1996. View at Publisher · View at Google Scholar · View at Scopus
  99. S. E. Myrdal, K. C. Johnson, and P. S. Steyger, “Cytoplasmic and intra-nuclear binding of gentamicin does not require endocytosis,” Hearing Research, vol. 204, no. 1-2, pp. 156–169, 2005. View at Publisher · View at Google Scholar · View at Scopus
  100. A. B. A. Kroese, A. Das, and A. J. Hudspeth, “Blockage of the transduction channels of hair cells in the bullfrog's sacculus by aminoglycoside antibiotics,” Hearing Research, vol. 37, no. 3, pp. 203–218, 1989. View at Google Scholar · View at Scopus
  101. A. Ricci, “Differences in mechano-transducer channel kinetics underlie tonotopic distribution of fast adaptation in auditory hair cells,” Journal of Neurophysiology, vol. 87, no. 4, pp. 1738–1748, 2002. View at Google Scholar · View at Scopus
  102. D. P. Corey and A. J. Hudspeth, “Ionic basis of the receptor potential in a vertebrate hair cell,” Nature, vol. 281, no. 5733, pp. 675–677, 1979. View at Google Scholar · View at Scopus
  103. J. E. Gale, W. Marcotti, H. J. Kennedy, C. J. Kros, and G. P. Richardson, “FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel,” Journal of Neuroscience, vol. 21, no. 18, pp. 7013–7025, 2001. View at Google Scholar · View at Scopus
  104. H. E. Farris, C. L. LeBlanc, J. Goswami, and A. J. Ricci, “Probing the pore of the auditory hair cell mechanotransducer channel in turtle,” Journal of Physiology, vol. 558, no. 3, pp. 769–792, 2004. View at Publisher · View at Google Scholar · View at Scopus
  105. T. Hayashida, H. Hiel, D. Dulon, J. P. Erre, A. Guilhaume, and J. M. Aran, “Dynamic changes following combined treatment with gentamicin and ethacrynic acid with and without acoustic stimulation. Cellular uptake and functional correlates,” Acta Oto-Laryngologica, vol. 108, no. 5-6, pp. 404–413, 1989. View at Google Scholar · View at Scopus
  106. A. J. Ricci, H. J. Kennedy, A. C. Crawford, and R. Fettiplace, “The transduction channel filter in auditory hair cells,” Journal of Neuroscience, vol. 25, no. 34, pp. 7831–7839, 2005. View at Publisher · View at Google Scholar · View at Scopus
  107. C. J. Kros, A. Rusch, and G. P. Richardson, “Mechano-electrical transducer currents in hair cells of the cultured neonatal mouse cochlea,” Proceedings of the Royal Society B, vol. 249, no. 1325, pp. 185–193, 1992. View at Google Scholar · View at Scopus
  108. D. Z. Z. He, S. Jia, and P. Dallas, “Mechanoelectrical transduction of adult outer hair cells studied in a gerbil hemicochlea,” Nature, vol. 429, no. 6993, pp. 766–770, 2004. View at Publisher · View at Google Scholar · View at Scopus
  109. A. J. Ricci, A. C. Crawford, and R. Fettiplace, “Tonotopic variation in the conductance of the hair cell mechanotransducer channel,” Neuron, vol. 40, no. 5, pp. 983–990, 2003. View at Publisher · View at Google Scholar · View at Scopus
  110. J. Garcia-Anoveros and A. Duggan, TRPA1 in Auditory and Nociceptive Organs, 2007.
  111. Y. Asai, J. R. Holt, and G. S.G. Géléoc, “A quantitative analysis of the spatiotemporal pattern of transient receptor potential gene expression in the developing mouse cochlea,” Journal of the Association for Research in Otolaryngology, vol. 11, no. 1, pp. 27–37, 2010. View at Publisher · View at Google Scholar
  112. M. P. Cuajungco, C. Grimm, and S. Heller, “TRP channels as candidates for hearing and balance abnormalities in vertebrates,” Biochimica et Biophysica Acta, vol. 1772, no. 8, pp. 1022–1027, 2007. View at Publisher · View at Google Scholar
  113. P. S. Steyger, “Cellular uptake of aminoglycosides,” Volta Review, vol. 105, no. 3, pp. 299–324, 2005. View at Google Scholar · View at Scopus
  114. S. E. Myrdal and P. S. Steyger, “TRPV1 regulators mediate gentamicin penetration of cultured kidney cells,” Hearing Research, vol. 204, no. 1-2, pp. 170–182, 2005. View at Publisher · View at Google Scholar · View at Scopus
  115. S. K. Moestrup, S. Cui, H. Vorum et al., “Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs,” Journal of Clinical Investigation, vol. 96, no. 3, pp. 1404–1413, 1995. View at Google Scholar · View at Scopus
  116. K. Mizuta, A. Saito, T. Watanabe et al., “Ultrastructural localization of megalin in the rat cochlear duct,” Hearing Research, vol. 129, no. 1-2, pp. 83–91, 1999. View at Publisher · View at Google Scholar · View at Scopus
  117. J. Tauris, E. I. Christensen, A. Nykjær, C. Jacobsen, C. M. Petersen, and T. Ovesen, “Cubilin and megalin Co-localize in the neonatal inner ear,” Audiology and Neurotology, vol. 14, no. 4, pp. 267–278, 2009. View at Publisher · View at Google Scholar
  118. M. Lenoir and J. L. Puel, “Dose-dependent changes in the rat cochlea following aminoglycoside intoxidation. II. Histological study,” Hearing Research, vol. 26, no. 2, pp. 199–209, 1987. View at Google Scholar · View at Scopus
  119. A. Forge, “Outer hair cell loss and supporting cell expansion following chronic gentamicin treatment,” Hearing Research, vol. 19, no. 2, pp. 171–182, 1985. View at Google Scholar · View at Scopus
  120. L. P. Rybak and C. A. Whitworth, “Ototoxicity: therapeutic opportunities,” Drug Discovery Today, vol. 10, no. 19, pp. 1313–1321, 2005. View at Publisher · View at Google Scholar · View at Scopus
  121. R. N. Abi-Hachem, A. Zine, and T. R. Van de Water, “The injured cochlea as a target for inflammatory processes, initiation of cell death pathways and application of related otoprotective strategies,” Recent Patents on CNS Drug Discovery, vol. 5, no. 2, pp. 147–163, 2010. View at Publisher · View at Google Scholar · View at Scopus
  122. E. M. Priuska and J. Schacht, “Formation of free radicals by gentamicin and iron and evidence for an iron/gentamicin complex,” Biochemical Pharmacology, vol. 50, no. 11, pp. 1749–1752, 1995. View at Publisher · View at Google Scholar · View at Scopus
  123. W. J. Clerici, K. Hensley, D. L. DiMartino, and D. A. Butterfield, “Direct detection of ototoxicant-induced reactive oxygen species generation in cochlear explants,” Hearing Research, vol. 98, no. 1-2, pp. 116–124, 1996. View at Publisher · View at Google Scholar · View at Scopus
  124. K. Hirose, D. M. Hockenbery, and E. W. Rubel, “Reactive oxygen species in chick hair cells after gentamicin exposure in vitro,” Hearing Research, vol. 104, no. 1-2, pp. 1–14, 1997. View at Publisher · View at Google Scholar · View at Scopus
  125. S. H. Sha and J. Schacht, “Stimulation of free radical formation by aminoglycoside antibiotics,” Hearing Research, vol. 128, no. 1-2, pp. 112–118, 1999. View at Publisher · View at Google Scholar · View at Scopus
  126. C. Thomas, M. M. Mackey, A. A. Diaz, and D. P. Cox, “Hydroxyl radical is produced via the Fenton reaction in submitochondrial particles under oxidative stress: implications for diseases associated with iron accumulation,” Redox Report, vol. 14, no. 3, pp. 102–108, 2009. View at Publisher · View at Google Scholar · View at Scopus
  127. S. H. Sha and J. Schacht, “Formation of reactive oxygen species following bioactivation of gentamicin,” Free Radical Biology and Medicine, vol. 26, no. 3-4, pp. 341–347, 1999. View at Publisher · View at Google Scholar · View at Scopus
  128. P. -W. Cheng, S. -H. Liu, Y. -H. Young, and S. -Y. Lin-Shiau, “D-Methionine attenuated cisplatin-induced vestibulotoxicity through altering ATPase activities and oxidative stress in guinea pigs,” Toxicology and Applied Pharmacology, vol. 215, no. 2, pp. 228–236, 2006. View at Publisher · View at Google Scholar
  129. P. W. Cheng, S. H. Liu, C. J. Hsu, and S. Y. Lin-Shiau, “Correlation of increased activities of Na+, K+-ATPase and Ca2+-ATPase with the reversal of cisplatin ototoxicity induced by D-methionine in guinea pigs,” Hearing Research, vol. 205, no. 1-2, pp. 102–109, 2005. View at Publisher · View at Google Scholar · View at Scopus
  130. J. M. C. Gutteridge and B. Halliwell, “The measurement and mechanism of lipid peroxidation in biological systems,” Trends in Biochemical Sciences, vol. 15, no. 4, pp. 129–135, 1990. View at Google Scholar · View at Scopus
  131. B. Halliwell and J. M. C. Gutteridge, “Role of free radicals and catalytic metal ions in human disease: an overview,” Methods in Enzymology, vol. 186, pp. 1–85, 1990. View at Publisher · View at Google Scholar · View at Scopus
  132. J. M. C. Gutteridge and B. Halliwell, “Free radicals and antioxidants in the year 2000. A historical look to the future,” Annals of the New York Academy of Sciences, vol. 899, pp. 136–147, 2000. View at Google Scholar · View at Scopus
  133. T. Yamasoba, A. L. Nuttall, C. Harris, Y. Raphael, and J. M. Miller, “Role of glutathione in protection against noise-induced hearing loss,” Brain Research, vol. 784, no. 1-2, pp. 82–90, 1998. View at Publisher · View at Google Scholar · View at Scopus
  134. T. Yamasoba, C. Harris, F. Shoji, R. J. Lee, A. L. Nuttall, and J. M. Miller, “Influence of intense sound exposure on glutathione synthesis in the cochlea,” Brain Research, vol. 804, no. 1, pp. 72–78, 1998. View at Publisher · View at Google Scholar · View at Scopus
  135. S. W. Jeong, L. S. Kim, D. Hur, W. Y. Bae, J. R. Kim, and J. H. Lee, “Gentamicin-induced spiral ganglion cell death: apoptosis mediated by ROS and the JNK signaling pathway,” Acta Oto-Laryngologica, vol. 130, no. 6, pp. 670–678, 2010. View at Publisher · View at Google Scholar · View at Scopus
  136. A. G. Cheng, L. L. Cunningham, and E. W. Rubel, “Mechanisms of hair cell death and protection,” Current Opinion in Otolaryngology and Head and Neck Surgery, vol. 13, no. 6, pp. 343–348, 2005. View at Publisher · View at Google Scholar · View at Scopus
  137. M. X. Guan, “Mitochondrial 12S rRNA mutations associated with aminoglycoside ototoxicity,” Mitochondrion, vol. 11, no. 2, pp. 237–245, 2011. View at Google Scholar
  138. P. H. Krammer, “CD95's deadly mission in the immune system,” Nature, vol. 407, no. 6805, pp. 789–795, 2000. View at Publisher · View at Google Scholar · View at Scopus
  139. D. F. Suen, K. L. Norris, and R. J. Youle, “Mitochondrial dynamics and apoptosis,” Genes and Development, vol. 22, no. 12, pp. 1577–1590, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. M. E. Peter and P. H. Krammer, “The CD95(APO-1/Fas) DISC and beyond,” Cell Death and Differentiation, vol. 10, no. 1, pp. 26–35, 2003. View at Publisher · View at Google Scholar · View at Scopus
  141. D. Brenner and T. W. Mak, “Mitochondrial cell death effectors,” Current Opinion in Cell Biology, vol. 21, no. 6, pp. 871–877, 2009. View at Publisher · View at Google Scholar · View at Scopus
  142. A. Strasser, L. O'Connor, and V. M. Dixit, “Apoptosis signaling,” Annual Review of Biochemistry, vol. 69, pp. 217–245, 2000. View at Publisher · View at Google Scholar · View at Scopus
  143. C. Borner, “The Bcl-2 protein family: sensors and checkpoints for life-or-death decisions,” Molecular Immunology, vol. 39, no. 11, pp. 615–647, 2003. View at Publisher · View at Google Scholar · View at Scopus
  144. A. Gross, J. Jockel, M. C. Wei, and S. J. Korsmeyer, “Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis,” EMBO Journal, vol. 17, no. 14, pp. 3878–3885, 1998. View at Publisher · View at Google Scholar · View at Scopus
  145. H. Harada and S. Grant, “Apoptosis regulators,” Reviews in Clinical and Experimental Hematology, vol. 7, no. 2, pp. 117–138, 2003. View at Google Scholar · View at Scopus
  146. L. Lalier, P. F. Cartron, P. Juin et al., “Bax activation and mitochondrial insertion during apoptosis,” Apoptosis, vol. 12, no. 5, pp. 887–896, 2007. View at Publisher · View at Google Scholar · View at Scopus
  147. T. Lindsten, W. X. Zong, and C. B. Thompson, “Defining the role of the Bcl-2 family of proteins in the nervous system,” Neuroscientist, vol. 11, no. 1, pp. 10–15, 2005. View at Publisher · View at Google Scholar · View at Scopus
  148. Z. N. Oltvai, C. L. Milliman, and S. J. Korsmeyer, “Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death,” Cell, vol. 74, no. 4, pp. 609–619, 1993. View at Publisher · View at Google Scholar · View at Scopus
  149. H. Xiang, Y. Kinoshita, C. M. Knudson, S. J. Korsmeyer, P. A. Schwartzkroin, and R. S. Morrison, “Bax involvement in p53-mediated neuronal cell death,” Journal of Neuroscience, vol. 18, no. 4, pp. 1363–1373, 1998. View at Google Scholar · View at Scopus
  150. D. A. Mangiardi, K. McLaughlin-Williamson, K. E. May, E. P. Messana, D. C. Mountain, and D. A. Cotanche, “Progression of hair cell ejection and molecular markers of apoptosis in the avian cochlea following gentamicin treatment,” Journal of Comparative Neurology, vol. 475, no. 1, pp. 1–18, 2004. View at Publisher · View at Google Scholar · View at Scopus
  151. J. E. Lee, T. Nakagawa, T. S. Kim et al., “Signaling pathway for apoptosis of vestibular hair cells of Mice due to aminoglycosides,” Acta Oto-Laryngologica, vol. 124, supplement 551, pp. 69–74, 2004. View at Publisher · View at Google Scholar
  152. J. I. Matsui, J. E. Gale, and M. E. Warchol, “Critical signaling events during the aminoglycoside-induced death of sensory hair cells in vitro,” Journal of Neurobiology, vol. 61, no. 2, pp. 250–266, 2004. View at Publisher · View at Google Scholar · View at Scopus
  153. N. Dehne, U. Rauen, H. de Groot, and J. Lautermann, “Involvement of the mitochondrial permeability transition in gentamicin ototoxicity,” Hearing Research, vol. 169, no. 1-2, pp. 47–55, 2002. View at Publisher · View at Google Scholar · View at Scopus
  154. T. Nakagawa and H. Yamane, “Cytochrome c redistribution in apoptosis of guinea pig vestibular hair cells,” Brain Research, vol. 847, no. 2, pp. 357–359, 1999. View at Publisher · View at Google Scholar · View at Scopus
  155. L. L. Cunningham, J. I. Matsui, M. E. Warchol, and E. W. Rubel, “Overexpression of Bcl-2 prevents neomycin-induced hair cell death and caspase-9 activation in the adult mouse utricle in vitro,” Journal of Neurobiology, vol. 60, no. 1, pp. 89–100, 2004. View at Publisher · View at Google Scholar · View at Scopus
  156. C. Bonny, A. Oberson, S. Negri, C. Sauser, and D. F. Schorderet, “Cell-permeable peptide inhibitors of JNK. Novel blockers of β-cell death,” Diabetes, vol. 50, no. 1, pp. 77–82, 2001. View at Google Scholar · View at Scopus
  157. M. Dickens, J. S. Rogers, J. Cavanagh et al., “A cytoplasmic inhibitor of the JNK signal transduction pathway,” Science, vol. 277, no. 5326, pp. 693–696, 1997. View at Publisher · View at Google Scholar · View at Scopus
  158. Y. T. Ip and R. J. Davis, “Signal transduction by the c-Jun N-terminal kinase (JNK) - From inflammation to development,” Current Opinion in Cell Biology, vol. 10, no. 2, pp. 205–219, 1998. View at Publisher · View at Google Scholar · View at Scopus
  159. A. Zine and T. R. Van De Water, “The MAPK/JNK signalling pathways offers potential therapeutic targets for the prevention of acquired deafness,” Current Drug Targets: CNS and Neurological Disorders, vol. 3, no. 4, pp. 325–332, 2004. View at Publisher · View at Google Scholar · View at Scopus
  160. J. Liu and A. Lin, “Role of JNK activation in apoptosis: a double-edged sword,” Cell Research, vol. 15, no. 1, pp. 36–42, 2005. View at Publisher · View at Google Scholar · View at Scopus
  161. J. Wang, T. R. Van De Water, C. Bonny, F. De Ribaupierre, J. L. Puel, and A. Zine, “A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss,” Journal of Neuroscience, vol. 23, no. 24, pp. 8596–8607, 2003. View at Google Scholar · View at Scopus
  162. U. Pirvola, L. Xing-Qun, J. Virkkala et al., “Rescue of hearing, auditory hair cells, and neurons by CEP-1347/KT7 an inhibitor of c-Jun N-terminal kinase activation,” Journal of Neuroscience, vol. 20, no. 1, pp. 43–50, 2000. View at Google Scholar · View at Scopus
  163. X. Liu, C. N. Kim, J. Yang, R. Jemmerson, and X. Wang, “Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c,” Cell, vol. 86, no. 1, pp. 147–157, 1996. View at Publisher · View at Google Scholar · View at Scopus
  164. H. R. Stennicke and G. S. Salvesen, “Caspases—controlling intracellular signals by protease zymogen activation,” Biochimica et Biophysica Acta, vol. 1477, no. 1-2, pp. 299–306, 2000. View at Publisher · View at Google Scholar
  165. M. Muzio, B. R. Stockwell, H. R. Stennicke, G. S. Salvesen, and V. M. Dixit, “An induced proximity model for caspase-8 activation,” Journal of Biological Chemistry, vol. 273, no. 5, pp. 2926–2930, 1998. View at Publisher · View at Google Scholar · View at Scopus
  166. L. L. Cunningham, A. G. Cheng, and E. W. Rubel, “Caspase activation in hair cells of the mouse utricle exposed to neomycin,” Journal of Neuroscience, vol. 22, no. 19, pp. 8532–8540, 2002. View at Google Scholar · View at Scopus
  167. A. G. Cheng, L. L. Cunningham, and E. W. Rubel, “Hair cell death in the avian basilar papilla: characterization of the in vitro model and caspase activation,” Journal of the Association for Research in Otolaryngology, vol. 4, no. 1, pp. 91–105, 2003. View at Publisher · View at Google Scholar
  168. J. Wang, S. Ladrech, R. Pujol, P. Brabet, T. R. Van De Water, and J. L. Puel, “Caspase inhibitors, but not c-Jun NH2-terminal kinase inhibitor treatment, prevent cisplatin-induced hearing loss,” Cancer Research, vol. 64, no. 24, pp. 9217–9224, 2004. View at Publisher · View at Google Scholar · View at Scopus
  169. D. Bodmer, D. Brors, K. Pak, M. Bodmer, and A. F. Ryan, “Gentamicin-induced hair cell death is not dependent on the apoptosis receptor Fas,” Laryngoscope, vol. 113, no. 3, pp. 452–455, 2003. View at Publisher · View at Google Scholar · View at Scopus
  170. J. Yuan and B. A. Yankner, “Caspase activity sows the seeds of neuronal death,” Nature Cell Biology, vol. 1, no. 2, pp. E44–45, 1999. View at Google Scholar · View at Scopus
  171. E. H. Y. Cheng, D. G. Kirsch, R. J. Clem et al., “Conversion of Bcl-2 to a bax-like death effector by caspases,” Science, vol. 278, no. 5345, pp. 1966–1968, 1997. View at Publisher · View at Google Scholar · View at Scopus
  172. Y. A. Lazebnik, S. H. Kaufmann, S. Desnoyers, G. G. Poirier, and W. C. Earnshaw, “Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE,” Nature, vol. 371, no. 6495, pp. 346–347, 1994. View at Publisher · View at Google Scholar · View at Scopus
  173. D. G. Kirsch, A. Doseff, B. N. Chau et al., “Caspase-3-dependent cleavage of Bcl-2 promotes release of cytochrome c,” Journal of Biological Chemistry, vol. 274, no. 30, pp. 21155–21161, 1999. View at Publisher · View at Google Scholar · View at Scopus
  174. S. Kothakota, T. Azuma, C. Reinhard et al., “Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis,” Science, vol. 278, no. 5336, pp. 294–298, 1997. View at Publisher · View at Google Scholar · View at Scopus
  175. J. B. Kim, J. Y. Jung, J. C. Ahn, C. K. Rhee, and H. J. Hwang, “Antioxidant and anti-apoptotic effect of melatonin on the vestibular hair cells of rat utricles,” Clinical and Experimental Otorhinolaryngology, vol. 2, no. 1, pp. 6–12, 2009. View at Publisher · View at Google Scholar · View at Scopus
  176. A. Caelers, V. Radojevic, J. Traenkle, Y. Brand, and D. Bodmer, “Stress and survival pathways in the mammalian cochlea,” Audiology and Neurotology, vol. 15, no. 5, pp. 282–290, 2010. View at Publisher · View at Google Scholar
  177. J. Momiyama, T. Hashimoto, A. Matsubara, K. Futai, A. Namba, and H. Shinkawa, “Leupeptin, a calpain inhibitor, protects inner ear hair cells from aminoglycoside ototoxicity,” Tohoku Journal of Experimental Medicine, vol. 209, no. 2, pp. 89–97, 2006. View at Publisher · View at Google Scholar · View at Scopus
  178. A. Forge and L. Li, “Apoptotic death of hair cells in mammalian vestibular sensory epithelia,” Hearing Research, vol. 139, no. 1-2, pp. 97–115, 2000. View at Publisher · View at Google Scholar · View at Scopus
  179. J. A. Williams and N. Holder, “Cell turnover in neuromasts of zebrafish larvae,” Hearing Research, vol. 143, no. 1-2, pp. 171–181, 2000. View at Publisher · View at Google Scholar · View at Scopus
  180. J. I. Matsui, A. Haque, D. Huss et al., “Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo,” Journal of Neuroscience, vol. 23, no. 14, pp. 6111–6122, 2003. View at Google Scholar · View at Scopus
  181. T. Nakagawa, T. S. Kim, N. Murai et al., “A novel technique for inducing local inner ear damage,” Hearing Research, vol. 176, no. 1-2, pp. 122–127, 2003. View at Publisher · View at Google Scholar · View at Scopus
  182. T. Okuda, K. Sugahara, T. Takemoto, H. Shimogori, and H. Yamashita, “Inhibition of caspases alleviates gentamicin-induced cochlear damage in guinea pigs,” Auris Nasus Larynx, vol. 32, no. 1, pp. 33–37, 2005. View at Publisher · View at Google Scholar · View at Scopus
  183. K. Sugahara, E. W. Rubel, and L. L. Cunningham, “JNK signaling in neomycin-induced vestibular hair cell death,” Hearing Research, vol. 221, no. 1-2, pp. 128–135, 2006. View at Publisher · View at Google Scholar · View at Scopus
  184. D. Bodmer, D. Brors, M. Bodmer, and A. F. Ryan, “Rescue of auditory hair cells from ototoxicity by CEP-11 004, an inhibitor of the JNK signaling pathway,” Laryngo- Rhino- Otologie, vol. 81, no. 12, pp. 853–856, 2002. View at Publisher · View at Google Scholar · View at Scopus
  185. M. Nakamagoe, K. Tabuchi, I. Uemaetomari, B. Nishimura, and A. Hara, “Estradiol protects the cochlea against gentamicin ototoxicity through inhibition of the JNK pathway,” Hearing Research, vol. 261, no. 1-2, pp. 67–74, 2010. View at Publisher · View at Google Scholar · View at Scopus
  186. J. Ylikoski, L. Xing-Qun, J. Virkkala, and U. Pirvola, “Blockade of c-Jun N-terminal kinase pathway attenuates gentamicin-induced cochlear and vestibular hair cell death,” Hearing Research, vol. 166, no. 1-2, pp. 33–43, 2002. View at Publisher · View at Google Scholar · View at Scopus
  187. S. C. Pfannenstiel, M. Praetorius, P. K. Plinkert, D. E. Brough, and H. Staecker, “Bcl-2 gene therapy prevents aminoglycoside-induced degeneration of auditory and vestibular hair cells,” Audiology and Neurotology, vol. 14, no. 4, pp. 254–266, 2009. View at Publisher · View at Google Scholar
  188. Y. H. Liu, X. M. Ke, Y. Qin, Z. P. Gu, and S. F. Xiao, “Adeno-associated virus-mediated Bcl-xL prevents aminoglycoside-induced hearing loss in mice,” Chinese Medical Journal, vol. 120, no. 14, pp. 1236–1240, 2007. View at Google Scholar · View at Scopus
  189. R. I. Morimoto, “Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging,” Genes and Development, vol. 22, no. 11, pp. 1427–1438, 2008. View at Publisher · View at Google Scholar · View at Scopus
  190. L. L. Cunningham and C. S. Brandon, “Heat shock inhibits both aminoglycoside- and cisplatin-induced sensory hair cell death,” Journal of the Association for Research in Otolaryngology, vol. 7, no. 3, pp. 299–307, 2006. View at Publisher · View at Google Scholar
  191. M. Taleb, C. S. Brandon, F. -S. Lee, M. I. Lomax, W. H. Dillmann, and L. L. Cunningham, “Hsp70 inhibits aminoglycoside-induced hair cell death and is necessary for the protective effect of heat shock,” Journal of the Association for Research in Otolaryngology, vol. 9, no. 3, pp. 277–289, 2008. View at Publisher · View at Google Scholar
  192. M. Taleb, C. S. Brandon, F. S. Lee, K. C. Harris, W. H. Dillmann, and L. L. Cunningham, “Hsp70 inhibits aminoglycoside-induced hearing loss and cochlear hair cell death,” Cell Stress and Chaperones, vol. 14, no. 4, pp. 427–437, 2009. View at Publisher · View at Google Scholar · View at Scopus
  193. K. Tabuchi, K. Pak, E. Chavez, and A. F. Ryan, “Role of inhibitor of apoptosis protein in gentamicin-induced cochlear hair cell damage,” Neuroscience, vol. 149, no. 1, pp. 213–222, 2007. View at Publisher · View at Google Scholar · View at Scopus
  194. D. Dulon, H. Hiel, C. Aurousseau, J. P. Erre, and J. M. Aran, “Pharmacokinetics of gentamicin in the sensory hair cells of the organ of Corti: rapid uptake and long term persistence,” Comptes Rendus de l'Academie des Sciences Series III, vol. 316, no. 7, pp. 682–687, 1993. View at Google Scholar · View at Scopus
  195. M. Olsson and B. Zhivotovsky, “Caspases and cancer,” Cell Death and Differentiation, vol. 18, no. 9, pp. 1441–1449, 2011. View at Google Scholar
  196. P. Sinswat, W. J. Wu, S. H. Sha, and J. Schacht, “Protection from ototoxicity of intraperitoneal gentamicin in guinea pig,” Kidney International, vol. 58, no. 6, pp. 2525–2532, 2000. View at Publisher · View at Google Scholar · View at Scopus
  197. B. B. Song and J. Schacht, “Variable efficacy of radical scavengers and iron chelators to attenuate gentamicin ototoxicity in guinea pig in vivo,” Hearing Research, vol. 94, no. 1-2, pp. 87–93, 1996. View at Publisher · View at Google Scholar · View at Scopus
  198. W. J. Wu, S. H. Sha, J. D. McLaren, K. Kawamoto, Y. Raphael, and J. Schacht, “Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat,” Hearing Research, vol. 158, no. 1-2, pp. 165–178, 2001. View at Publisher · View at Google Scholar · View at Scopus
  199. E. Lecain, B. Omri, F. Behar-Cohen, P. T. B. Huy, and P. Crisanti, “The role of PKCζ in amikacin-induced apoptosis in the cochlea: prevention by aspirin,” Apoptosis, vol. 12, no. 2, pp. 333–342, 2007. View at Publisher · View at Google Scholar · View at Scopus
  200. S. H. Sha and J. Schacht, “Salicylate attenuates gentamicin-induced ototoxicity,” Laboratory Investigation, vol. 79, no. 7, pp. 807–813, 1999. View at Google Scholar · View at Scopus
  201. F. Behnoud, K. Davoudpur, and M. T. Goodarzi, “Can aspirin protect or at least attenuate gentamicin ototoxicity in humans?” Saudi Medical Journal, vol. 30, no. 9, pp. 1165–1169, 2009. View at Google Scholar · View at Scopus
  202. Y. Chen, W. G. Huang, D. J. Zha et al., “Aspirin attenuates gentamicin ototoxicity: from the laboratory to the clinic,” Hearing Research, vol. 226, no. 1-2, pp. 178–182, 2007. View at Publisher · View at Google Scholar · View at Scopus
  203. S. H. Sha, J. H. Qiu, and J. Schacht, “Aspirin to prevent gentamicin-induced hearing loss,” The New England Journal of Medicine, vol. 354, no. 17, pp. 1856–1857, 2006. View at Publisher · View at Google Scholar · View at Scopus
  204. E. N. Myers and J. M. Bernstein, “Salicylate ototoxicity; a clinical and experimental study,” Archives of Otolaryngology, vol. 82, no. 5, pp. 483–493, 1965. View at Google Scholar · View at Scopus
  205. G. D. Chen, M. H. Kermany, A. D'Elia et al., “Too much of a good thing: long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity,” Hearing Research, vol. 265, no. 1-2, pp. 63–69, 2010. View at Publisher · View at Google Scholar · View at Scopus
  206. M. D. Hilty, C. A. Romshe, and P. V. Delamater, “Reye's syndrome and hyperaminoacidemia,” Journal of Pediatrics, vol. 84, no. 3, pp. 362–365, 1974. View at Google Scholar · View at Scopus
  207. R. D. K. Reye, G. Morgan, and J. Baral, “Encephalopathy and fatty degeneration of the viscera. A disease entity in childhood,” The Lancet, vol. 282, no. 7311, pp. 749–752, 1963. View at Google Scholar · View at Scopus
  208. I. Tanret and D. Duh, “The Reye syndrome,” Journal de Pharmacie de Belgique, vol. 1, pp. 13–15, 2011. View at Google Scholar
  209. S. H. Sha, G. Zajic, C. J. Epstein, and J. Schacht, “Overexpression of copper/zinc-superoxide dismutase protects from kanamycin-induced hearing loss,” Audiology and Neuro-Otology, vol. 6, no. 3, pp. 117–123, 2001. View at Publisher · View at Google Scholar
  210. L. Feldman, S. Efrati, E. Eviatar et al., “Gentamicin-induced ototoxicity in hemodialysis patients is ameliorated by N-acetylcysteine,” Kidney International, vol. 72, no. 3, pp. 359–363, 2007. View at Publisher · View at Google Scholar · View at Scopus
  211. K. C. M. Campbell, R. P. Meech, J. J. Klemens et al., “Prevention of noise- and drug-induced hearing loss with d-methionine,” Hearing Research, vol. 226, no. 1-2, pp. 92–103, 2007. View at Publisher · View at Google Scholar · View at Scopus
  212. S. H. Sha and J. Schacht, “Antioxidants attenuate gentamicin-induced free radical formation in vitro and ototoxicity in vivo: D-methionine is a potential protectant,” Hearing Research, vol. 142, no. 1-2, pp. 34–40, 2000. View at Publisher · View at Google Scholar · View at Scopus
  213. M. Takumida, M. Anniko, A. Shimizu, and H. Watanabe, “Neuroprotection of vestibular sensory cells from gentamicin ototoxicity obtained using nitric oxide synthase inhibitors, reactive oxygen species scavengers, brain-derived neurotrophic factors and calpain inhibitors,” Acta Oto-Laryngologica, vol. 123, no. 1, pp. 8–13, 2003. View at Publisher · View at Google Scholar · View at Scopus
  214. B. J. Conlon, J. M. Aran, J. P. Erre, and D. W. Smith, “Attenuation of aminoglycoside-induced cochlear damage with the metabolic antioxidant α-lipoic acid,” Hearing Research, vol. 128, no. 1-2, pp. 40–44, 1999. View at Publisher · View at Google Scholar · View at Scopus
  215. A. R. Fetoni, B. Sergi, A. Ferraresi, G. Paludetti, and D. Troiani, “α-Tocopherol protective effects on gentamicin ototoxicity: an experimental study,” International Journal of Audiology, vol. 43, no. 3, pp. 166–171, 2004. View at Publisher · View at Google Scholar
  216. A. R. Fetoni, B. Sergi, E. Scarano, G. Paludetti, A. Ferraresi, and D. Troiani, “Protective effects of α-tocopherol against gentamicin-induced oto-vestibulo toxicity: an experimental study,” Acta Oto-Laryngologica, vol. 123, no. 2, pp. 192–197, 2003. View at Publisher · View at Google Scholar
  217. B. Sergi, A. R. Fetoni, A. Ferraresi et al., “The role of antioxidants in protection from ototoxic drugs,” Acta Oto-Laryngologica, vol. 124, no. 552, supplement, pp. 42–45, 2004. View at Google Scholar
  218. S. L. Garetz, D. J. Rhee, and J. Schacht, “Sulfhydryl compounds and antioxidants inhibit cytotoxicity to outer hair cells of a gentamicin metabolite in vitro,” Hearing Research, vol. 77, no. 1-2, pp. 75–80, 1994. View at Publisher · View at Google Scholar · View at Scopus
  219. H. W. Jung, S. O. Chang, C. S. Kim, C. S. Rhee, and D. H. Lim, “Effects of Ginkgo biloba extract on the cochlear damage induced by local gentamicin installation in guinea pigs,” Journal of Korean Medical Science, vol. 13, no. 5, pp. 525–528, 1998. View at Google Scholar · View at Scopus
  220. A. M. Wang et al., “Tanshinone (Salviae miltiorrhizae extract) preparations attenuate aminoglycoside-induced free radical formation in vitro and ototoxicity in vivo,” Antimicrobial Agents and Chemotherapy, vol. 47, no. 6, pp. 1836–1841, 2003. View at Google Scholar
  221. T. Erdem, O. Ozturan, M. Iraz, M. C. Miman, and E. Olmez, “Dose-dependent dual effect of melatonin on ototoxicity induced by amikacin in adult rats,” European Archives of Oto-Rhino-Laryngology, vol. 262, no. 4, pp. 314–321, 2005. View at Publisher · View at Google Scholar · View at Scopus
  222. L. F. Ye, Z. Z. Tao, Q. Q. Hua et al., “Protective effect of melatonin against gentamicin ototoxicity,” Journal of Laryngology and Otology, vol. 123, no. 6, pp. 598–602, 2009. View at Publisher · View at Google Scholar · View at Scopus
  223. M. A. Lopez-Gonzalez, J. M. Guerrero, R. Torronteras, C. Osuna, and F. Delgado, “Ototoxicity caused by aminoglycosides is ameliorated by melatonin without interfering with the antibiotic capacity of the drugs,” Journal of Pineal Research, vol. 28, no. 1, pp. 26–33, 2000. View at Publisher · View at Google Scholar · View at Scopus
  224. K. Kawamoto, S. H. Sha, R. Minoda et al., “Antioxidant gene therapy can protect hearing and hair cells from ototoxicity,” Molecular Therapy, vol. 9, no. 2, pp. 173–181, 2004. View at Publisher · View at Google Scholar · View at Scopus
  225. S. L. McFadden, D. Ding, D. Salvemini, and R. J. Salvi, “M40403, a superoxide dismutase mimetic, protects cochlear hair cells from gentamicin, but not cisplatin toxicity,” Toxicology and Applied Pharmacology, vol. 186, no. 1, pp. 46–54, 2003. View at Publisher · View at Google Scholar
  226. M. S. Asplund, A. Lidian, B. Linder, M. Takumida, and M. Anniko, “Protective effect of edaravone against tobramycin-induced ototoxicity,” Acta Oto-Laryngologica, vol. 129, no. 1, pp. 8–13, 2009. View at Publisher · View at Google Scholar · View at Scopus
  227. S. Bonabi, A. Caelers, A. Monge, A. Huber, and D. Bodmer, “Resveratrol protects auditory hair cells from gentamicin toxicity,” Ear, Nose and Throat Journal, vol. 87, no. 10, pp. 570–573, 2008. View at Google Scholar · View at Scopus
  228. S. L. Garetz, R. A. Altschuler, and J. Schacht, “Attenuation of gentamicin ototoxicity by glutathione in the guinea pig in vivo,” Hearing Research, vol. 77, no. 1-2, pp. 81–87, 1994. View at Publisher · View at Google Scholar · View at Scopus
  229. B. J. Conlon and D. W. Smith, “Topical aminoglycoside ototoxicity: attempting to protect the cochlea,” Acta Oto-Laryngologica, vol. 120, no. 5, pp. 596–599, 2000. View at Publisher · View at Google Scholar · View at Scopus
  230. E. N. Maudonnet, J. A. A. De Oliveira, M. Rossato, and M. A. Hyppolito, “Gentamicin attenuates gentamicin-induced ototoxicity - Self-protection,” Drug and Chemical Toxicology, vol. 31, no. 1, pp. 11–25, 2008. View at Publisher · View at Google Scholar · View at Scopus
  231. J. A. A. De Oliveira, D. M. Canedo, M. Rossato, and M. H. De Andrade, “Self-protection against aminoglycoside ototoxicity in guinea pigs,” Otolaryngology—Head and Neck Surgery, vol. 131, no. 3, pp. 271–279, 2004. View at Publisher · View at Google Scholar · View at Scopus
  232. A. C. Suryadevara, H. H. Wanamaker, and A. Pack, “The effects of sound conditioning on gentamicin-induced vestibulocochlear toxicity in gerbils,” Laryngoscope, vol. 119, no. 6, pp. 1166–1170, 2009. View at Publisher · View at Google Scholar · View at Scopus
  233. A. S. Basile, J. M. Huang, C. Xie, D. Webster, C. Berlin, and P. Skolnick, “N-Methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss,” Nature Medicine, vol. 2, no. 12, pp. 1338–1343, 1996. View at Publisher · View at Google Scholar · View at Scopus
  234. A. S. Basile, A. M. Brichta, B. D. Harris, D. Morse, D. Coling, and P. Skolnick, “Dizocilpine attenuates streptomycin-induced vestibulotoxicity in rats,” Neuroscience Letters, vol. 265, no. 2, pp. 71–74, 1999. View at Publisher · View at Google Scholar · View at Scopus
  235. W. J. O'Sullivan, “Stability constants of metal complexes,” in Data for Biochemical Research, D. C. E. R. M. C. Dawson and A . K. M. J. W. H. Elliott, Eds., Oxford Clarendon Press, Oxford, UK, 1969. View at Google Scholar
  236. C. F. Babbs and M. G. Steiner, “Detection and quantitation of hydroxyl radical using dimethyl sulfoxide as molecular probe,” Methods in Enzymology, vol. 186, pp. 137–147, 1990. View at Publisher · View at Google Scholar · View at Scopus
  237. S. H. Sha and J. Schacht, “Are aminoglycoside antibiotics excitotoxic?” NeuroReport, vol. 9, no. 17, pp. 3893–3895, 1998. View at Google Scholar · View at Scopus
  238. R. Pujol, “Lateral and medial efferents: a double neurochemical mechanism to protect and regulate inner and outer hair cell function in the cochlea,” British Journal of Audiology, vol. 28, no. 4-5, pp. 185–191, 1994. View at Google Scholar · View at Scopus
  239. E. Hokkanen, “The aggravating effect of some antibiotics on the neuromuscular blockade in myasthenia gravis,” Acta Neurologica Scandinavica, vol. 40, pp. 346–352, 1964. View at Google Scholar
  240. R. W. Barrons, “Drug-induced neuromuscular blockade and myasthenia gravis,” Pharmacotherapy, vol. 17, no. 6, pp. 1220–1232, 1997. View at Google Scholar · View at Scopus
  241. C. Lee et al., “Neuromuscular block by neomycin in the cat,” Canadian Anaesthetists' Society Journal, vol. 23, no. 5, pp. 527–533, 1976. View at Google Scholar
  242. J. S. Kass and W. X. Shandera, “Nervous system effects of antituberculosis therapy,” CNS Drugs, vol. 24, no. 8, pp. 655–667, 2010. View at Publisher · View at Google Scholar · View at Scopus
  243. J. F. Fiekers, “Effects of the aminoglycoside antibiotics, streptomycin and neomycin, on neuromuscular transmission. I. Presynaptic considerations,” Journal of Pharmacology and Experimental Therapeutics, vol. 225, no. 3, pp. 487–495, 1983. View at Google Scholar · View at Scopus
  244. J. F. Fiekers, “Effects of the aminoglycoside antibiotics, streptomycin and neomycin, on neuromuscular transmission. II. Postsynaptic considerations,” Journal of Pharmacology and Experimental Therapeutics, vol. 225, no. 3, pp. 496–502, 1983. View at Google Scholar · View at Scopus
  245. A. Alharazneh, L. Luk, M. Huth et al., “Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity,” PLoS ONE, vol. 6, no. 7, article e22347, 2011. View at Publisher · View at Google Scholar
  246. I. Lopez, V. Honrubia, S. C. Lee et al., “The protective effect of brain-derived neurotrophic factor after gentamicin ototoxicity,” American Journal of Otology, vol. 20, no. 3, pp. 317–324, 1999. View at Google Scholar · View at Scopus
  247. M. Takumida and M. Anniko, “Brain-derived neurotrophic factor and nitric oxide synthase inhibitor protect the vestibular organ against gentamicin ototoxicity,” Acta Oto-Laryngologica, vol. 122, no. 1, pp. 10–15, 2002. View at Publisher · View at Google Scholar · View at Scopus
  248. R. S. Ruan, S. K. Leong, I. Mark, and K. H. Yeoh, “Effects of BDNF and NT-3 on hair cell survival in guinea pig cochlea damaged by kanamycin treatment,” NeuroReport, vol. 10, no. 10, pp. 2067–2071, 1999. View at Google Scholar · View at Scopus
  249. C. He, S. J. Kang, Y. Dou et al., “Ciliary neurotrophic factor antagonizes gentamicin-induced alterations of electric potentials in auditory pathway in guinea pigs,” Acta Pharmacologica Sinica, vol. 17, no. 6, pp. 493–496, 1996. View at Google Scholar · View at Scopus
  250. R. Kuang, G. Hever, G. Zajic et al., “Glial cell line-derived neurotrophic factor. Potential for otoprotection,” Annals of the New York Academy of Sciences, vol. 884, pp. 270–291, 1999. View at Google Scholar · View at Scopus
  251. L. N. Gillespie, G. M. Clark, P. F. Bartlett, and P. L. Marzella, “BDNF-induced survival of auditory neurons in vivo: cessation of treatment leads to accelerated loss of survival effects,” Journal of Neuroscience Research, vol. 71, no. 6, pp. 785–790, 2003. View at Publisher · View at Google Scholar · View at Scopus
  252. D. Ding, H. Jiang, and R. J. Salvi, “Mechanisms of rapid sensory hair-cell death following co-administration of gentamicin and ethacrynic acid,” Hearing Research, vol. 259, no. 1-2, pp. 16–23, 2010. View at Publisher · View at Google Scholar · View at Scopus
  253. D. Ding, S. L. McFadden, R. W. Browne, and R. J. Salvi, “Late dosing with ethacrynic acid can reduce gentamicin concentration in perilymph and protect cochlear hair cells,” Hearing Research, vol. 185, no. 1-2, pp. 90–96, 2003. View at Publisher · View at Google Scholar · View at Scopus
  254. R. H. Mathog and W. J. Klein, “Ototoxicity of ethacrynic acid and aminoglycoside antibiotics in uremia,” The New England Journal of Medicine, vol. 280, no. 22, pp. 1223–1224, 1969. View at Google Scholar · View at Scopus
  255. M. Takumida and M. Anniko, “Isosorbide delays gentamicin-induced vestibular sensory cell death,” ORL, vol. 67, no. 5, pp. 276–281, 2005. View at Publisher · View at Google Scholar
  256. M. Duan, K. Agerman, P. Ernfors, and B. Canlon, “Complementary roles of neurotrophin 3 and a N-methyl-D-aspartate antagonist in the protection of noise and aminoglycoside-induced ototoxicity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 13, pp. 7597–7602, 2000. View at Publisher · View at Google Scholar · View at Scopus
  257. K. Kawamoto, M. Yagi, T. Stöver, S. Kanzaki, and Y. Raphael, “Hearing and hair cells are protected by adenoviral gene therapy with TGF-β1 and GDNF,” Molecular Therapy, vol. 7, no. 4, pp. 484–492, 2003. View at Publisher · View at Google Scholar · View at Scopus
  258. M. Suzuki, M. Yagi, J. N. Brown, A. L. Miller, J. M. Miller, and Y. Raphael, “Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity,” Gene Therapy, vol. 7, no. 12, pp. 1046–1054, 2000. View at Google Scholar · View at Scopus
  259. M. Yagi, E. Magal, Z. Sheng, K. A. Ang, and Y. Raphael, “Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor,” Human Gene Therapy, vol. 10, no. 5, pp. 813–823, 1999. View at Publisher · View at Google Scholar · View at Scopus
  260. R. Fettiplace, A. J. Ricci, and C. M. Hackney, “Clues to the cochlear amplifier from the turtle ear,” Trends in Neurosciences, vol. 24, no. 3, pp. 169–175, 2001. View at Publisher · View at Google Scholar · View at Scopus
  261. A. J. Hudspeth, Y. Choe, A. D. Mehta, and P. Martin, “Putting ion channels to work: mechanoelectrical transduction, adaptation, and amplification by hair cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 22, pp. 11765–11772, 2000. View at Publisher · View at Google Scholar · View at Scopus
  262. K. McQuillen, “The bacterial surface IV. Effect of streptomycin on the electrophoretic mobility of escherichia coli and Staphylococcus aureus,” Biochimica et Biophysica Acta, vol. 7, no. 1, pp. 54–60, 1951. View at Google Scholar
  263. R. E.W. Hancock and A. Bell, “Antibiotic uptake into gram-negative bacteria,” European Journal of Clinical Microbiology and Infectious Diseases, vol. 7, no. 6, pp. 713–720, 1988. View at Google Scholar
  264. G. G. Jackson, V. T. Lolans, and G. L. Daikos, “The inductive role of ionic binding in the bactericidal and postexposure effects of aminoglycoside antibiotics with implications for dosing,” Journal of Infectious Diseases, vol. 162, no. 2, pp. 408–413, 1990. View at Google Scholar · View at Scopus