Cisplatin-induced apoptotic cell death in Mongolian gerbil cochlea

Shaheen Ara Alam, Katsuhisa Ikeda, Takeshi Ohshima, Masaaki Suzuki, Tetsuaki Kawase, Toshihiko Kikuchi, Tomonori Takasaka

Research output: Contribution to journalArticlepeer-review

128 Citations (Scopus)

Abstract

Cisplatin is well known to cause cochleotoxicity. In order to determine the underlying mechanisms of cisplatin-induced cell death in the cochlea, we investigated the apoptotic changes and the expression of bcl-2 family proteins controlling apoptosis. Mongolian gerbils were administered 4 mg/kg/day cisplatin consecutively for 5 days. The cisplatin-treated animals showed a significant deterioration in the responses of both distortion product otoacoustic emissions and the endocochlear potential as compared with those of the age-matched controls, suggesting outer hair cell and stria vascularis dysfunction. The presence of DNA fragmentation revealed by a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling method was recognized in the organ of Corti, the spiral ganglion, and the stria vascularis in the cisplatin-treated animals whereas almost negative results were obtained in the control animals. The nuclear morphology obtained by Hoechst 33342 staining revealed pyknotic and condensed nuclei, confirming the presence of the characteristic features of apoptosis. A significant increase and reduction in the number of bax- and bcl-2-positive cells, respectively, following cisplatin treatment was observed in the cells of the organ of Corti, the spiral ganglion, and the lateral wall. These findings suggest a critical role for bcl-2 family proteins in the regulation of apoptotic cell death induced by cisplatin. The underlying mechanisms of the cisplatin-induced cell death are discussed. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)28-38
Number of pages11
JournalHearing Research
Volume141
Issue number1-2
DOIs
Publication statusPublished - 2000 Mar 1

Keywords

  • Apoptosis
  • Bax
  • Bcl-2
  • Distortion product otoacoustic emission
  • Endocochlear potential
  • Hoechst 33342
  • TUNEL

ASJC Scopus subject areas

  • Sensory Systems

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