Endogenous protection against oxidative stress caused by cisplatin: role of superoxide dismutase.
CONCLUSIONS
The administration of cisplatin induces the activation of superoxide dismutase (SOD) as a response to oxidative stress in the cochleae of Sprague-Dawley rats and this activation is proportional to the activation of the intrinsic pathway of apoptosis.


OBJECTIVE
To determine the role of the antioxidant endogenous mechanism in the preservation of cochlear integrity and function in an experimental model of cisplatin ototoxicity.


METHODS
Sixteen Sprague-Dawley rats were studied at 7 days after intraperitoneal injection of CDDP (n = 8) or 10 ml/kg NaCl 0.9% w/v in the control group (n = 8) by means of auditory steady-state responses. These findings were compared with the expression of SOD and caspase-3/7 and caspase-9 activities.


RESULTS
Groups receiving cisplatin showed increased auditory thresholds after injection of cisplatin and control groups maintained normal hearing. Measurements of caspase-3/7 and caspase-9 showed a significant increase in cisplatin-treated rats. A significantly increased activity of total SOD in whole cochlear extracts was observed in animals from the CDDP groups vs control animals. Likewise, differences between CDDP groups were also statistically significant.
González-García
José Angel
JA
Servicio de Otorrinolaringología, Instituto Oncológico Kutxa-Onkologikoa, Paseo Dr Begiristain 119, San Sebastián, Guipúzcoa. jagonzalez@onkologikoa.org
Nevado
Julián
J
García-Berrocal
José Ramón
JR
Sánchez-Rodríguez
Carolina
C
Trinidad
Almudena
A
Sanz
Ricardo
R
Ramírez-Camacho
Rafael
R
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000097:blood; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism; D003124:Colorimetry / Q000379:methods; D006311:Hearing Disorders / Q000517:prevention & control; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*
D000970:Antineoplastic Agents; D013482:Superoxide Dismutase; D020169:Caspases; D002945:Cisplatin