Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish
Article first published online: 6 DEC 2011
Copyright © 2011 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 2, pages 125–133, February 2013
How to Cite
Choi, J., Im, G. J., Chang, J., Chae, S. W., Lee, S. H., Kwon, S.-Y., Chung, A.-Y., Park, H.-C. and Jung, H. H. (2013), Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish. J. Appl. Toxicol., 33: 125–133. doi: 10.1002/jat.1729
- Issue published online: 21 DEC 2012
- Article first published online: 6 DEC 2011
- Manuscript Revised: 27 JUL 2011
- Manuscript Accepted: 27 JUL 2011
- Manuscript Received: 27 JAN 2011
- HEI-OC1 cells;
Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation. In this study, the effect of apocynin was investigated in a cochlear organ of Corti-derived cell line, HEI-OC1 cells, and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects of apocynin, HEI-OC1 cells were treated with various concentrations of apocynin and a 20 µm concentration of cisplatin, simultaneously. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin-induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin-induced apoptotic features on Hoechst 33258 staining in the HEI-OC1 cells. Treatment of the HEI-OC1 cells with 100 µm of apocynin, significantly decreased caspase-3 activity. Treatment of the cells with a 100 µm concentration of apocynin and a 20 µm concentration of cisplatin significantly decreased the intracellular ROS production. In the in vivo study, apocynin significantly decreased the TUNEL reaction and prevented cisplatin-induced hair cell loss of the neuromasts in the transgenic zebrafish at low concentrations (125 and 250 µm). These findings suggest that apocynin has antioxidative effects and prevents cisplatin-induced apoptotic cell death in HEI-OC1 cells as well as in zebrafish. Copyright © 2011 John Wiley & Sons, Ltd.