Protective role of L‐ascorbic acid, N‐acetylcysteine and apocynin on neomycin‐induced hair cell loss in Zebrafish

Abstract

Hair cells are highly sensitive to environmental insults and other therapeutic drugs. The adverse effects of drugs such as aminoglycosides can cause hair cell death and lead to hearing loss and imbalance. The objective of the present study was to evaluate the protective activity of L-ascorbic acid, N-acetylcysteine (NAC) and apocynin on neomycin-induced hair cell damage in zebrafish (Danio rerio) larvae at 5 days post fertilization (dpf). Results showed that the loss of hair cells within the neuromasts of the lateral lines after neomycin exposure was evidenced by a significantly lower number of neuromasts labeled with fluorescent dye FM1-43FX observed under a microscope. Co-administration with L-ascorbic acid, NAC and apocynin protected neomycin-induced hair cell loss within the neuromasts. Moreover, these three compounds reduced the production of reactive oxygen species (ROS) in neuromasts exposed to neomycin, indicating that their antioxidant action is involved. In contrast, the neuromasts were labeled with specific fluorescent dye Texas-red conjugated with neomycin to detect neomycin uptake. Interestingly, the uptake of neomycin into hair cells was not influenced by these three antioxidant compounds. These data imply that prevention of hair cell damage against neomycin by L-ascorbic acid, NAC and apocynin might be associated with inhibition of excessive ROS production, but not related to modulating neomycin uptake. Our findings conclude that L-ascorbic acid, NAC and apocynin could be used as therapeutic drugs to protect aminoglycoside-induced listening impairment after further confirmatory studies.

Sodium Selenite Acts as an Otoprotectant against Neomycin-Induced Hair Cell Damage in a Zebrafish Model

“…However, it is known that the injection of 10 −3 mol/L neomycin (2 ml) into the unilateral cochlea via the round window membrane induces the loss of all homolateral cochlear and vestibular hair cells and hearing and vestibular function abnormalities in adult C57BL/6 mice [ 41 ]. ROS formation by neomycin is reported to play a role in neomycin-induced ototoxicity, and antioxidant compounds is assumed to inhibit intracellular apoptotic pathways triggered by neomycin [ 42 , 43 ]. Our previous reports also demonstrated that neomycin elevated ROS formation and induced apoptosis [ 44 ].…”

Sensory hair cell death and regeneration in fishes

“…One strategy for preventing damage to hair cells is to administer otoprotective drugs that counteract cellular injury from otherwise beneficial drugs (Coffin et al, 2010 ; Ou et al, 2010 ; Esterberg et al, 2013 ). Otoprotectants mainly work by interfering with antibiotic uptake (Hailey et al, 2012 ; Ou et al, 2012 ) or inhibiting generation of reactive oxygen species (Le Prell et al, 2007 ; Wu et al, 2014 ). The antioxidant epicatechin protects both mammalian and zebrafish hair cells against cisplatin damage and decreases reactive oxygen species generation (Kim et al, 2008 ).…”

Real-time visualization of oxidative stress-mediated neurodegeneration of individual spinal motor neurons in vivo

“…We next investigated the impact of antioxidant treatment upon KR-mediated ROS generation. The potent ROS scavenging compound Nacetylcysteine (NAC) has been shown to successfully rescue overall cellular and oxidative stress [35] , [36] , [37] . Application of increasing H 2 O 2 concentrations (1 mM, 2 mM, 5 mM, and 10 mM) led to significant and dose-dependent increase in ROS-mediated fluorescence in 3 dpf zebrafish embryos ( Fig.…”