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

Abstract

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.

Protective effect of resveratrol against cisplatin-induced ototoxicity in HEI-OC1 auditory cells

“…Resveratrol's anti-oxidative effect is a 9% reduction of cisplatin-induced ROS, which is lower than that observed in acetyl cysteine (26.1%), glutathione (36.1%), tocopherol (35.7%), metformin (17%), and klotho (15%) [7,[18][19][20]. In this study, resveratrol showed significantly less protection compared with glutathione and a-tocopherol (Fig.…”

The Safety Pharmacology of Auditory Function

“…Similar to the mechanism apparent with aminoglycosides, it appears these compounds produce free radicals which induce apoptosis in the auditory outer hair cells (Choe et al 2004;Choi et al 2013;Qu et al 2012;Yumusakhuylu et al 2012). These compounds also produce auditory neural damage by causing detachment of the myelin sheath surrounding the spiral ganglia, which is also thought to be a result of damage from free radicals (Lee et al 2004;van Ruijven et al 2005).…”

Dexmedetomidine Preconditioning Attenuates Cisplatin-Induced Ototoxicity in Zebrafish

“…Preconditioning was performed for 150 minutes, and exposure to 1 mM of cisplatin [4] was conducted for 6 hours; the control group, which did not receive any treatment, was monitored for 8 hours. After the cisplatin treatment, the medium was removed and the dish was washed three times with phosphate buffer solution (PBS), followed by quantification of hair cells in the neuromasts.…”

“…Hong et al [3] showed that the utilisation of inhibitory drugs such as edaravone reduced hair cell damage and Choi et al [4] reported that substances extracted from vanilla such as apocynin imparted protective effects on neurons. However, because these drugs are not commonly used in head and neck surgery, their clinical importance is not clear.…”