Display options
Cite
Dalian D, Haiyan J, Yong F, et al. OTOTOXIC EFFECTS OF CARBOPLATIN IN ORGANOTYPIC CULTURES IN CHINCHILLAS AND RATS. J Otol. 2012;7(2):92-101doi: 10.1016/S1672-2930(12)50023-1.
Dalian, D., Haiyan, J., Yong, F., Salvi, R., Someya, S., & Tanokura, M. (2012). OTOTOXIC EFFECTS OF CARBOPLATIN IN ORGANOTYPIC CULTURES IN CHINCHILLAS AND RATS. Journal of otology, 7(2), 92-101. https://doi.org/10.1016/S1672-2930(12)50023-1
Dalian, Ding, et al. "OTOTOXIC EFFECTS OF CARBOPLATIN IN ORGANOTYPIC CULTURES IN CHINCHILLAS AND RATS." Journal of otology vol. 7,2 (2012): 92-101. doi: https://doi.org/10.1016/S1672-2930(12)50023-1
Dalian D, Haiyan J, Yong F, Salvi R, Someya S, Tanokura M. OTOTOXIC EFFECTS OF CARBOPLATIN IN ORGANOTYPIC CULTURES IN CHINCHILLAS AND RATS. J Otol. 2012 Dec;7(2):92-101. doi: 10.1016/S1672-2930(12)50023-1. PMID: 25593588; PMCID: PMC4291553.
Copy Download .nbib Format: NLM
Share it on

J Otol. 2012 Dec;7(2):92-101. doi: 10.1016/S1672-2930(12)50023-1.

OTOTOXIC EFFECTS OF CARBOPLATIN IN ORGANOTYPIC CULTURES IN CHINCHILLAS AND RATS.

Journal of otology

Ding Dalian, Jiang Haiyan, Fu Yong, Richard Salvi, Shinichi Someya, Masaru Tanokura

Affiliations

  1. Center for Hearing and Deafness, State University of New York at Buffalo ; Graduate School of Agricultural and Life Sciences, University of Tokyo.
  2. Center for Hearing and Deafness, State University of New York at Buffalo.
  3. Departments of Aging and Geriatric Research, Division of Biology of Aging, University of Florida.
  4. Graduate School of Agricultural and Life Sciences, University of Tokyo.

PMID: 25593588 PMCID: PMC4291553 DOI: 10.1016/S1672-2930(12)50023-1

Abstract

Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin ototoxicity, the chinchilla stands out as highly susceptible. Moreover, carboplatin causes an unusual gradient of cell death in chinchillas. Moderate doses selectively damage type I spiral ganglion neurons (SGN) and inner hair cells (IHC) and the lesion tends to be relatively uniform along the length of the cochlea. Higher doses eventually damage outer hair cells (OHC), but the lesion follows the traditional gradient in which damage is more severe in the base than the apex. While carboplatin ototoxicity has been well documented in adult animals in vivo, little is known about its in vitro toxicity. To elucidate the ototoxic effects of carboplatin in vitro, we prepared cochlear and vestibular organotypic cultures from postnatal day 3 rats and adult chinchillas. Chinchilla cochlear and vestibular cultures were treated with carboplatin concentrations ranging from 50 µM to 10 mM for 48 h. Consistent with in vivo data, carboplatin selectively damaged IHC at low concentrations (50-100 µM). Surprisingly, IHC loss decreased at higher doses and IHC were intact at doses exceeding 500 µM. The mechanisms underlying this nonlinear response are unclear but could be related to a decrease in carboplatin uptake via active transport mechanisms (e.g., copper). Unlike the cochlea, the carboplatin dose-response function increased with dose with the highest dose destroying all chinchilla vestibular hair cells. Cochlear hair cells and auditory nerve fibers in rat cochlear organotypic cultures were unaffected by carboplatin concentrations <10 µM; however, the damage in OHC were more severe than IHC once the dose reached 100 µM. A dose at 500 µM destroyed all the cochlear hair cells, but hair cell loss decreased at high concentrations and nearly all the cochlear hair cells were present at the highest dose, 5 mM. Unlike the nonlinear dose-response seen with cochlear hair cells, rat auditory nerve fiber and spiral ganglion losses increased with doses above 50 µM with the highest dose destroying virtually all SGN. The remarkable species differences seen in vitro suggest that chinchilla IHC and type I SGN posse some unique biological mechanism that makes them especially vulnerable to carboplatin toxicity.

Keywords: Carboplatin; organotypic culture; ototoxicity

References

  1. Audiology. 1997 Nov-Dec;36(6):301-11 - PubMed
  2. Drug Saf. 1995 Oct;13(4):228-44 - PubMed
  3. Int J Toxicol. 2003 Sep-Oct;22(5):335-42 - PubMed
  4. Klin Padiatr. 2002 Jul-Aug;214(4):149-52 - PubMed
  5. Hear Res. 1998 Jun;120(1-2):121-32 - PubMed
  6. Pharmacol Toxicol. 1995 Jun;76(6):386-94 - PubMed
  7. J Laryngol Otol. 1993 Jul;107(7):585-9 - PubMed
  8. Auris Nasus Larynx. 1989;16(1):13-21 - PubMed
  9. Drug Intell Clin Pharm. 1988 Nov;22(11):843-9 - PubMed
  10. J Biol Chem. 2012 May 25;287(22):18674-86 - PubMed
  11. Scanning Microsc. 1994 Mar;8(1):97-106 - PubMed
  12. Scand Audiol Suppl. 1999;51:1-12 - PubMed
  13. Brain Res Mol Brain Res. 2001 Sep 10;93(1):18-26 - PubMed
  14. J Appl Toxicol. 2005 Sep-Oct;25(5):374-82 - PubMed
  15. Am J Otol. 1997 Sep;18(5):559-71 - PubMed
  16. Mol Cancer Ther. 2002 Aug;1(10 ):821-9 - PubMed
  17. Hear Res. 1997 May;107(1-2):67-82 - PubMed
  18. Arch Otorhinolaryngol. 1985;242(1):77-81 - PubMed
  19. Cancer Metastasis Rev. 2007 Mar;26(1):71-83 - PubMed
  20. Bone Marrow Transplant. 1998 Oct;22(7):669-74 - PubMed
  21. Laryngorhinootologie. 1993 Jan;72(1):24-7 - PubMed
  22. Oncogene. 2006 Jul 6;25(29):4056-66 - PubMed
  23. Am J Physiol Renal Physiol. 2007 Jun;292(6):F1710-7 - PubMed
  24. J Biol Chem. 2004 Nov 5;279(45):46393-9 - PubMed
  25. Hear Res. 1996 Sep 1;98(1-2):116-24 - PubMed
  26. Eur J Cancer. 2006 Mar;42(4):492-500 - PubMed
  27. Hear Res. 2011 Dec;282(1-2):196-203 - PubMed
  28. Hear Res. 1994 May;75(1-2):93-102 - PubMed
  29. J Clin Oncol. 1996 Jul;14(7):2101-12 - PubMed
  30. Gan To Kagaku Ryoho. 1987 Sep;14(9):2682-7 - PubMed
  31. J Anal Toxicol. 2008 Mar;32(2):140-6 - PubMed
  32. Ann Neurol. 1995 Jul;38(1):30-7 - PubMed
  33. Chemotherapy. 2002 May;48(2):82-7 - PubMed
  34. Am J Physiol Renal Physiol. 2005 Sep;289(3):F514-20 - PubMed
  35. Eur J Neurosci. 1996 Sep;8(9):1897-905 - PubMed
  36. Mol Pharmacol. 2004 Oct;66(4):817-23 - PubMed
  37. Hear Res. 2001 Sep;159(1-2):14-22 - PubMed
  38. Cancer Res. 2006 Jun 1;66(11):5836-46 - PubMed
  39. Hear Res. 2007 Apr;226(1-2):129-39 - PubMed
  40. Toxicol Appl Pharmacol. 2001 Jul 1;174(1):27-34 - PubMed
  41. Ann Otol Rhinol Laryngol. 1988 Mar-Apr;97(2 Pt 1):133-7 - PubMed
  42. Cancer Res. 1984 Apr;44(4):1693-7 - PubMed
  43. Exp Hematol. 1985;13 Suppl 16:101-5 - PubMed
  44. Neurotoxicology. 2006 Jan;27(1):22-30 - PubMed
  45. Int J Toxicol. 2005 Nov-Dec;24(6):443-9 - PubMed
  46. Cancer Treat Rev. 1985 Sep;12 Suppl A:51-7 - PubMed
  47. Laryngoscope. 2003 Jun;113(6):994-9 - PubMed
  48. Oncol Rep. 2007 Oct;18(4):987-91 - PubMed
  49. Biomed Environ Sci. 2005 Jun;18(3):198-206 - PubMed
  50. Hear Res. 2002 Mar;165(1-2):19-29 - PubMed
  51. J Neurosci. 1995 Jul;15(7 Pt 2):5079-87 - PubMed
  52. Scanning Microsc. 1995 Mar;9(1):271-80; discussion 280-1 - PubMed
  53. J Toxicol Sci. 1988 Jul;13 Suppl 2:1-21 - PubMed
  54. Anat Rec (Hoboken). 2012 Nov;295(11):1851-67 - PubMed
  55. Cancer Res. 2007 May 15;67(10 ):4860-8 - PubMed
  56. Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14298-302 - PubMed
  57. Hear Res. 2000 Sep;147(1-2):261-74 - PubMed
  58. Med Oncol. 2003;20(3):237-45 - PubMed
  59. Curr Opin Chem Biol. 2002 Apr;6(2):171-80 - PubMed
  60. Clin Cancer Res. 1997 Nov;3(11):2063-74 - PubMed
  61. Cancer Chemother Pharmacol. 1982;9(3):140-7 - PubMed
  62. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2005 May;19(10):457-60 - PubMed
  63. Cancer Res. 1996 Feb 15;56(4):706-9 - PubMed
  64. Crit Rev Oncol Hematol. 2005 Jan;53(1):13-23 - PubMed
  65. Eur J Cancer Clin Oncol. 1987 Sep;23(9):1391-7 - PubMed
  66. Otolaryngol Head Neck Surg. 1986 Apr;94(4):458-70 - PubMed
  67. Mol Pharmacol. 2006 Jul;70(1):23-9 - PubMed
  68. Apoptosis. 2007 Oct;12 (10 ):1901-9 - PubMed
  69. Hear Res. 2010 Jan;259(1-2):16-23 - PubMed
  70. Laryngoscope. 2007 Dec;117(12):2183-6 - PubMed
  71. Hear Res. 2003 Nov;185(1-2):90-6 - PubMed
  72. Hear Res. 2002 Nov;173(1-2):1-9 - PubMed
  73. Audiol Neurootol. 2000 Sep-Oct;5(5):263-6 - PubMed
  74. J Clin Oncol. 1989 May;7(5):651-61 - PubMed
  75. Hear Res. 1999 Oct;136(1-2):139-50 - PubMed
  76. Cancer Treat Rev. 1987 Dec;14(3-4):389-95 - PubMed
  77. J Otolaryngol. 1994 Jun;23(3):151-9 - PubMed
  78. J Biol Chem. 2002 Nov 29;277(48):46736-42 - PubMed
  79. Laryngoscope. 1994 Apr;104(4):488-93 - PubMed
  80. Audiol Neurootol. 1997 May-Jun;2(3):155-67 - PubMed
  81. Bull Exp Biol Med. 2006 Apr;141(4):437-9 - PubMed
  82. J Pediatr Hematol Oncol. 2008 Feb;30(2):130-4 - PubMed
  83. Acta Otolaryngol Suppl. 1995;519:60-5 - PubMed
  84. Cancer Lett. 2006 Mar 8;234(1):34-9 - PubMed
  85. Hear Res. 1997 Oct;112(1-2):199-215 - PubMed
  86. Hear Res. 2002 Feb;164(1-2):115-26 - PubMed
  87. Ann N Y Acad Sci. 1999 Nov 28;884:152-70 - PubMed
  88. Cell Transplant. 2002;11(1):47-54 - PubMed
  89. Acta Otorhinolaryngol Ital. 2002 Feb;22(1):14-8 - PubMed
  90. Neuroscience. 2003;120(1):191-205 - PubMed
  91. Clin Exp Otorhinolaryngol. 2011 Mar;4(1):11-7 - PubMed
  92. Eur J Cancer. 2003 May;39(8):1129-40 - PubMed
  93. Biochem Pharmacol. 2007 Jan 15;73(2):298-307 - PubMed
  94. Toxicol Appl Pharmacol. 1990 Mar 15;103(1):1-15 - PubMed
  95. J Clin Oncol. 2012 Apr 1;30(10):1034-41 - PubMed
  96. Hear Res. 2000 Dec;150(1-2):132-6 - PubMed
  97. Hear Res. 2003 Aug;182(1-2):48-55 - PubMed
  98. Kidney Int. 1999 Oct;56(4):1295-8 - PubMed
  99. Cancer Chemother Pharmacol. 1990;26(3):232-4 - PubMed
  100. J Assoc Res Otolaryngol. 2002 Mar;3(1):68-79 - PubMed
  101. Hear Res. 2000 Mar;141(1-2):28-38 - PubMed
  102. Cancer Chemother Pharmacol. 1987;19(2):155-8 - PubMed
  103. J Assoc Res Otolaryngol. 2008 Jun;9(2):178-90 - PubMed
  104. Neurotoxicology. 2011 Mar;32(2):233-41 - PubMed
  105. Hear Res. 1999 Dec;138(1-2):13-28 - PubMed
  106. Am J Physiol Renal Physiol. 2004 Sep;287(3):F543-9 - PubMed
  107. Nihon Hinyokika Gakkai Zasshi. 1989 Apr;80(4):517-25 - PubMed
  108. Hear Res. 2003 Jul;181(1-2):65-72 - PubMed
  109. Neurotoxicology. 2001 Apr;22(2):163-76 - PubMed
  110. Zhonghua Er Bi Yan Hou Ke Za Zhi. 2003 Apr;38(2):98-100 - PubMed
  111. Eur J Ophthalmol. 2010 Jul-Aug;20(4):745-51 - PubMed
  112. Pediatrics. 2010 Apr;125(4):e938-50 - PubMed
  113. Mol Cell Biochem. 2007 Jan;295(1-2):153-65 - PubMed
  114. Basic Clin Pharmacol Toxicol. 2004 May;94(5):245-51 - PubMed
  115. Neurosci Lett. 2006 Jan 9;392(1-2):22-6 - PubMed
  116. Mol Pharmacol. 2002 Nov;62(5):1154-9 - PubMed
  117. Mol Pharmacol. 2001 Apr;59(4):657-63 - PubMed
  118. Audiology. 1992;31(5):293-9 - PubMed
  119. Neuroreport. 1998 Aug 3;9(11):2609-14 - PubMed
  120. Cell Tissue Res. 2000 Oct;302(1):1-10 - PubMed
  121. Hear Res. 2005 Mar;201(1-2):121-31 - PubMed
  122. Childs Nerv Syst. 2011 Mar;27(3):407-13 - PubMed
  123. Drugs. 1989 Feb;37(2):162-90 - PubMed
  124. Cancer. 2009 Jul 15;115(14):3243-53 - PubMed
  125. Cancer Res. 1987 Dec 1;47(23):6297-301 - PubMed
  126. Mol Pharmacol. 2008 Feb;73(2):461-8 - PubMed
  127. Toxicol Sci. 1999 Feb;47(2):195-202 - PubMed

Publication Types

Grant support