Protection of Cisplatin Ototoxicity with a Novel Src Inhibitor

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The Ohio State University

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Cisplatin is a drug used to treat a variety of cancers. It induces apoptosis, or programmed cell death in tumor cells, thus reducing tumor size and growth. Although the goal of this chemotherapy drug is to kill harmful cancer cells, it also damages other cells, such as outer hair cells (OHCs), fundamental cells within the inner ear responsible for the sensation of hearing. The intracellular signaling molecule, Src, a protein tyrosine kinase, has been implicated as a major signaling molecule in some cancer cells. In cancer, Src is believed to be hyper-active, and triggers unchecked cell division. In the cochlea, the stress on the cell induced by cisplatin is believed to trigger Src-mediated apoptosis. For this experiment, sixteen rats were tested in order to determine if saracatinib, a Src inhibitor, can prevent cisplatin ototoxicity. Eight rats served as the experimental group, and were exposed to cisplatin along with saracatinib. The other eight rats received the vehicle solution without the saracatinib prior to cisplatin exposure. Hearing sensitivity was measured using the auditory brainstem response and distortion product otoacoustic emissions. All animals were administered the protective compound over the nine days by oral gavages. A dose of 12mg/kg of cisplatin was administered after the second day of the gavages. All animals were retested three days, then six days after the cisplatin treatment to determine if a change in hearing threshold was present.



Cisplatin Ototoxicity with a Src Inhibitor