a1 Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Madrid, Spain
a2 Department of Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain
a3 Department of Internal Medicine, Hospital Universitario Puerta de Hierro, Madrid, Spain
a4 Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid, Spain
a5 Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
a6 Department of Otorhinolaryngology and Research Unit, Hospital Universitario de Getafe, Madrid, Spain
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.
(Accepted December 30 2009)
(Online publication March 23 2010)
c1 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@example.com
Dr J R García-Berrocal takes responsibility for the integrity of the content of the paper.
Competing interests: None declared