title: 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.
authors.affiliation: Department of Physiology, Tzu Chi University, No. 701, Sec. 3, Chung Yang Rd., Hualien, 97004, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Wu
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Chi-Fang
authors.initials: CF
authors.lastname: Liu
authors.forename: Mallikarjuna
authors.initials: M
authors.lastname: Korivi
authors.forename: Hwei-Hsien
authors.initials: HH
authors.lastname: Chen
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Chan
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000111:Acetylcysteine / Q000494:pharmacology; D023401:Animal Use Alternatives; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008465:Mechanoreceptors / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018613:Microscopy, Confocal; D009355:Neomycin / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology
chemical_list: D000098:Acetophenones; D000900:Anti-Bacterial Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; C056165:acetovanillone; D009355:Neomycin; D001205:Ascorbic Acid; D000111:Acetylcysteine
keywords: L-ascorbic acid; N-acetylcysteine; apocynin; hair cell; ototoxicity; zebrafish