Western Kentucky University
New Platinum Compounds May Kill Cancer Without Causing Hearing Side-Effects
Institution
Western Kentucky University
Faculty Advisor/ Mentor
Michael E. Smith; J. David Monroe
Abstract
Platinum-based chemotherapy treatments such as cisplatin often produce the unfortunate side effect of hearing loss. This is due to their ototoxic effect of destroying the sensory hair cells of the inner ear that transduce sound vibrations into neural auditory signals. We first investigated whether hair cell loss occurs in the zebrafish inner ear after exposure to cisplatin. This data was then used as a positive control in a study of several novel platinum (II) compounds which exhibit anticancer activity, with the goal of finding novel compounds that kill cancer cells without damaging auditory hair cells. Zebrafish were microinjected with cisplatin at a concentration of 3.75 mg/kg of body weight and then 24 hours later had their hearing tested by recording auditory evoked potentials. Afterwards, their inner ears were dissected and their auditory end organs, the saccule and utricle, were removed. These tissues were then fluorescently stained with phalloidin, viewed under a microscope, and hair cell densities were determined in each end organ to assess hair cell loss. Cisplatin-injected zebrafish exhibited significant hearing loss between 250 and 1,000 Hz when compared to buffer-injected controls. In addition, cisplatin-injected fish had reduced saccular hair cell densities compared to controls, while no significant differences were exhibited in the utricle. We are currently testing the ototoxicity of phenanthriplatin in the zebrafish inner ear to see if it has reduced side effects relative to cisplatin. This project is the first step in using zebrafish as a model for evaluating whether novel platinum (II) compounds may be less ototoxic than cisplatin, and could lead to the development of less harmful forms of chemotherapy.
New Platinum Compounds May Kill Cancer Without Causing Hearing Side-Effects
Platinum-based chemotherapy treatments such as cisplatin often produce the unfortunate side effect of hearing loss. This is due to their ototoxic effect of destroying the sensory hair cells of the inner ear that transduce sound vibrations into neural auditory signals. We first investigated whether hair cell loss occurs in the zebrafish inner ear after exposure to cisplatin. This data was then used as a positive control in a study of several novel platinum (II) compounds which exhibit anticancer activity, with the goal of finding novel compounds that kill cancer cells without damaging auditory hair cells. Zebrafish were microinjected with cisplatin at a concentration of 3.75 mg/kg of body weight and then 24 hours later had their hearing tested by recording auditory evoked potentials. Afterwards, their inner ears were dissected and their auditory end organs, the saccule and utricle, were removed. These tissues were then fluorescently stained with phalloidin, viewed under a microscope, and hair cell densities were determined in each end organ to assess hair cell loss. Cisplatin-injected zebrafish exhibited significant hearing loss between 250 and 1,000 Hz when compared to buffer-injected controls. In addition, cisplatin-injected fish had reduced saccular hair cell densities compared to controls, while no significant differences were exhibited in the utricle. We are currently testing the ototoxicity of phenanthriplatin in the zebrafish inner ear to see if it has reduced side effects relative to cisplatin. This project is the first step in using zebrafish as a model for evaluating whether novel platinum (II) compounds may be less ototoxic than cisplatin, and could lead to the development of less harmful forms of chemotherapy.