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Heat shock protein 70 and cellular disturbances in cochlear cisplatin ototoxicity model

Published online by Cambridge University Press:  23 March 2010

J R García-Berrocal ,
J Nevado ,
J Á González-García ,
C Sánchez-Rodríguez ,
R Sanz ,
A Trinidad ,
P España ,
M J Citores  and
R Ramírez-Camacho
J R García-Berrocal*
Affiliation:
Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Madrid, Spain
J Nevado
Affiliation:
Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
J Á González-García
Affiliation:
Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Madrid, Spain
C Sánchez-Rodríguez
Affiliation:
Department of Otorhinolaryngology and Research Unit, Hospital Universitario de Getafe, Madrid, Spain
R Sanz
Affiliation:
Department of Otorhinolaryngology and Research Unit, Hospital Universitario de Getafe, Madrid, Spain
A Trinidad
Affiliation:
Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Madrid, Spain
P España
Affiliation:
Department of Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain
M J Citores
Affiliation:
Department of Internal Medicine, Hospital Universitario Puerta de Hierro, Madrid, Spain
R Ramírez-Camacho
Affiliation:
Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Madrid, Spain
*
Address for correspondence: Dr José Ramón García-Berrocal, Servicio de Otorrinolaringología, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28222 Majadahonda, Madrid, Spain. Fax: +34 91 3730535 E-mail: [email protected]
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Abstract

Background:

Exposure to cisplatin leads to cochlear cell death by apoptosis; these changes are most marked on the seventh day after exposure. Heat shock proteins are induced in inner ear cells in response to a variety of stimuli. This study examined the role of heat shock protein 70 in cisplatin-induced cochlear cell death.

Methods:

Fifty-six Sprague–Dawley rats were involved. Some were injected with cisplatin (5 mg/kg body weight), some with cisplatin plus the caspase inhibitor Z-Asp(OMe)-Glu(OMe)-Val-Asp(OME)-fluoromethylketone (5 mg/kg body weight) and others were left as controls (being injected only with saline). Seven days later, we examined the expression of heat shock protein 70 and several other apoptosis-related proteins within the rat cochlear cells; we also assessed total superoxide dismutase activity, auditory brainstem response and auditory steady state response.

Results:

Seven days after cisplatin injection, significantly increased expression of heat shock protein 70 was found within the rat cochleae. This correlated with increased executioner caspase levels, total superoxide dismutase activity and auditory brainstem response thresholds, and a significant elevation in auditory steady state response thresholds. Inhibition of caspase-3 activity significantly reduced cochlear heat shock protein 70 expression and total superoxide dismutase activity, and improved auditory brainstem response and auditory steady state response thresholds.

Conclusions:

Seven days after cisplatin exposure, we found disturbances of the cochlear cellular machinery involving heat shock protein 70, other apoptotic proteins and total superoxide dismutase.

Keywords

Cis-platinumOtotoxicityCochlea
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 124 , Issue 6 , June 2010 , pp. 599 - 609
Copyright
Copyright © JLO (1984) Limited 2010

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