Protective effects of apocynin on cisplatin-induced ototoxicity in an auditory cell line and in zebrafish

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.
Journal of applied toxicology : JAT   33(2): 125-133 (Journal)
Registered Authors
Park, Hae-Chul
apocynin, cisplatin, ototoxicity, HEI-OC1 cells, zebrafish
MeSH Terms
  • Acetophenones/pharmacology*
  • Animals
  • Animals, Genetically Modified
  • Antineoplastic Agents/toxicity*
  • Antioxidants/pharmacology*
  • Apoptosis/drug effects*
  • Caspase 3/metabolism
  • Cell Culture Techniques
  • Cell Line
  • Cell Survival/drug effects
  • Cisplatin/toxicity*
  • Dose-Response Relationship, Drug
  • Green Fluorescent Proteins/genetics
  • Hair Cells, Auditory/drug effects*
  • Hair Cells, Auditory/metabolism
  • Hair Cells, Auditory/pathology
  • Hearing Loss/chemically induced
  • Hearing Loss/metabolism
  • Hearing Loss/prevention & control
  • In Situ Nick-End Labeling
  • Mice
  • Microscopy, Fluorescence
  • Neurons/drug effects*
  • Neurons/metabolism
  • Neurons/pathology
  • Reactive Oxygen Species/metabolism
  • Zebrafish
22147442 Full text @ J. Appl. Toxicol.

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.

Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes