Endogenous protection against oxidative stress caused by cisplatin: role of superoxide dismutase

Abstract

Conclusion: 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. Objectives: 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.

Keywords::

• Ototoxicity
• reactive oxygen species
• inner ear
• chemoprotection
• cytoprotection
• apoptosis
• caspase

Acknowledgment

This study was supported by the Spanish Research Fund (FIS) PI05/0673.