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Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Ginkgo biloba extract (EGb 761) protects against cisplatin-induced ototoxicity in rats
Xinyan Huang1, Craig A Whitworth, Leonard P Rybak
1Division of Otolaryngology Head & Neck Surgery, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9662, USA.
Hypothesis:
A standardized Ginkgo biloba extract, EGb 761, may have protective effect against cisplatin-induced ototoxicity in rats.
Background:
Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. Cisplatin-induced ototoxicity has been correlated to depletion of the cochlear antioxidant system and increased lipid peroxidation. EGb 761 contains potent antioxidants capable of scavenging free radicals, inhibiting nitric oxide synthesis, reducing lipid peroxidation, and protecting against apoptosis. The purpose of this study was to investigate the effect of EGb 761 on cisplatin-induced ototoxicity in rats.
Methods:
Male Wistar rats were divided into four groups and were treated as follows: 1) vehicle control; 2) cisplatin (13 mg/kg, intraperitoneally) plus vehicle; 3) EGb 761 (200 mg/kg, intraperitoneally); and 4) EGb 761 plus cisplatin. Auditory brainstem responses (ABRs) were measured pretreatment and 72 hours posttreatment, and threshold shifts were analyzed. Endocochlear potentials (EPs) were also obtained at 72 hours posttreatment. Cochleae were harvested and processed for scanning electron microscopy after completion of auditory testing.
Results:
Cisplatin-treated rats showed significant ABR threshold shifts across all frequencies (click, and 2-, 4-, 8-, 16-, and 32-kHz tones) compared with each of the other groups (p < 0.001). Rats treated with EGb 761 plus cisplatin did not show significant ABR threshold shifts (p > 0.05). Similarly, the EPs of cisplatin-treated rats were decreased significantly approximately 50% in comparison with the other groups (p < 0.001). The EPs of EGb 761 plus cisplatin-treated rats were decreased less than 20% compared with vehicle control group or the EGb 761 only group (p < 0.01). The scanning electron microscopy observation indicated severe outer hair cell loss in the basal turn of cochleae of cisplatin-treated rats, whereas outer hair cells remained intact in the rats treated with EGb 761 plus cisplatin.
Conclusion:
These results demonstrate that EGb 761 protects against cisplatin-induced ototoxicity.