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Abstract
Conclusions: EGb761 treatment has a significant benefit with an early and preventive effect, reversing the deleterious effect of aging in the integrity of the rat cochlea, even in the late stage of the rat lifespan. Objectives: We previously reported a significant relationship between aging and apoptosis in the rat cochlea. This study was designed to investigate the effects of Ginkgo biloba leaf extract (EGb761) on age-associated cochlear caspase activation. Methods: Sprague-Dawley rats (n = 80) divided into two groups according to their age (4 months old, younger, YR, and 12 months old, aged-mature, AM) were treated with 100 mg/kg/day body weight of EGb761 extract dissolved in tap water for two periods: 4 and 12 months. Then cochleae were harvested to measure caspase activities, ATP levels, total superoxide dismutase (SOD) activity, and caspase-3 gene expression. Auditory steady-state responses (ASSR) threshold shifts were also measured before sacrifice of the rats. Results: EGb761 treatment prevents significantly aging-related caspase-induced activities within the cochleae in YR and AM rats. In the short EGb761 treatment, YR rats showed lower levels of caspase-3/7 than AM rats. In contrast, longer treatment did not show significant differences between YR and AM rats. Reduced caspase-3/7 activity in presence of EGb761 correlates with significant improvements of ASSR threshold shifts.
Acknowledgments
This study was supported by Spanish Fondo de Investigaciones Sanitarias, FIS, PI04/1718. Dr J. Nevado was a recipient of a research contract from Instituto de Salud Carlos III (FIS 99/3077, until July 2007). C. Sánchez-Rodríguez was a recipient of a research contract from Instituto de Salud Carlos III (since January 2009).
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.