The curcuminoid, EF-24, reduces cisplatin-mediated reactive oxygen species in zebrafish inner ear auditory and vestibular tissues

• Published in: Journal of clinical neuroscience Vol. 57; pp. 152 - 156
• Main Authors: Monroe, Jerry D., Millay, Matthew H., Patty, Blaine G., Smith, Michael E.
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.11.2018
• Subjects: Animals; Antineoplastic Agents - pharmacology; Benzylidene Compounds - pharmacology; Cisplatin; Cisplatin - pharmacology; Curcuminoid; Drug Antagonism; Hair Cells, Auditory - drug effects; Hair Cells, Auditory - metabolism; Hair Cells, Vestibular - drug effects; Hair Cells, Vestibular - metabolism; Inner ear; Piperidones - pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Tissue culture; Zebrafish; Tissue culture; Zebrafish; Reactive oxygen species; Cisplatin; Inner ear; Curcuminoid
• ISSN: 0967-5868; 1532-2653
• DOI: 10.1016/j.jocn.2018.09.002

•Reactive oxygen species release increases in cisplatin-treated zebrafish endorgans.•Reactive oxygen species production in cisplatin only samples is dosage dependent.•Curcuminoid treatment does not increase endorgan reactive oxygen species.•Curcuminoid treatment counteracts cisplatin reactive oxygen species production. Cisplatin is a widely used chemotherapy drug that can damage auditory and vestibular tissue and cause hearing and balance loss through the intracellular release of reactive oxygen species (ROS). Curcumin has anticancer efficacy and can also counteract cisplatin’s damaging effect against sensory tissue by scavenging intracellular ROS, but curcumin’s applicability is limited due to its low bioavailability. EF-24 is a synthetic curcumin analog that is more bioavailable than curcumin and can target cancer, but its effects against cisplatin-mediated ROS in auditory and vestibular tissue is currently unknown. In this study, we employed a novel zebrafish inner ear tissue culture system to determine if EF-24 counteracted cisplatin-mediated ROS release in two sensory endorgans, the saccule and the utricle. The zebrafish saccule is associated with auditory function and the utricle with vestibular function. Trimmed endorgans were placed in tissue culture media with a fluorescent reactive oxygen species indicator dye, and intracellular ROS release was measured using a spectrophotometer. We found that cisplatin treatment significantly increased ROS compared to controls, but that EF-24 treatment did not alter or even decreased ROS. Importantly, when equimolar cisplatin and EF-24 treatments are combined, ROS did not increase compared to controls. This suggests that EF-24 may be able to prevent intracellular ROS caused by cisplatin treatment in inner ear tissue.