The use of zebrafish for assessing ototoxic and otoprotective agents

Ton, Christopher; Parng, Chuenlei

doi:10.1016/j.heares.2005.05.005

Cited by 208 publications

(170 citation statements)

References 80 publications

(106 reference statements)

Supporting

Mentioning

165

Contrasting

Order By: Relevance

“…However, in our experience, the inability of 5 dpf zebrafish to survive for longer periods within 96-well plates limits the ability to test hair cell toxicity over longer durations in a toxicity screening protocol. Longer exposures can be done independent of a drug screen, as has been demonstrated effectively by Ton and Parng (2005), and certainly have an important role for evaluating candidate ototoxins.…”

Section: Discussionmentioning

confidence: 99%

“…The zebrafish lateral line is a powerful system for identifying and evaluating drugs that damage mechanoreceptive hair cells, such as those in the inner ear of mammals (Ton and Parng 2005;Chiu et al 2008). Due to the small size and optically clear body of larval zebrafish, hair cell damage can be rapidly assessed.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, due to the rapidity of experiments and high fecundity, zebrafish larvae are particularly valuable for thoroughly testing and modulating dose-response relationships. The zebrafish has been used effectively to examine hair cell toxicity and elucidate doseresponse relationships for aminoglycosides and cisplatin (Wiliams and Holder 2000;Harris et al 2003;Ton and Parng 2005;Owens et al 2009;Ou et al 2007). In addition, it has been used to screen for toxicity to hair cells in a library of FDA-approved drugs and bioactives (Chiu et al 2008).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hair Cell Toxicity in Anti-cancer Drugs: Evaluating an Anti-cancer Drug Library for Independent and Synergistic Toxic Effects on Hair Cells Using the Zebrafish Lateral Line

Hirose

Simon

2011

JARO

View full text Add to dashboard Cite

Inner ear hair cell loss is the most common pathology seen after ototoxic drug injury. While certain drugs such as aminoglycosides and cisplatin are well-known to have dramatic ototoxic effects, it is probable that there are other drugs that cause occult degrees of hair cell loss and lesser degrees of hearing loss. Anti-cancer drugs are particularly strong candidates due to their general cytotoxicity. We have screened a library of 88 anti-cancer drugs (National Cancer Institute Approved Oncology Drugs Set) for drugs that damage hair cells of the zebrafish lateral line. The screen identified four out of five known ototoxic drugs. The screen also identified four out of seven suspected ototoxic drugs (drugs that have isolated case reports of patients developing hearing loss after administration). Five additional drugs with no known ototoxicity were identified as potentially novel ototoxins. Additional dose-response curves were performed to evaluate relative toxicity. Since anti-cancer drugs are often used clinically in combination, we also performed dose-response curves for a variety of anticancer drug combinations and demonstrated synergistic toxicity in five out of ten drug combinations that we tested. These findings support the use of the zebrafish lateral line as a screening tool to detect ototoxic effects in drugs and also suggest that ototoxicity should be considered in terms of drug regimens rather than individual drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hair Cell Toxicity in Anti-cancer Drugs: Evaluating an Anti-cancer Drug Library for Independent and Synergistic Toxic Effects on Hair Cells Using the Zebrafish Lateral Line

Hirose

Simon

2011

JARO

View full text Add to dashboard Cite

show abstract

“…The zebrafish lateral line system has been established as a useful preparation for studies of hair cell death (e.g., Williams and Holder 2000; Harris et al 2003;Ton and Parng 2005;Coffin et al 2010). Lateral line hair cells cluster in sensory organs called neuromasts that are externally located on the head and body of the animal (Metcalf et al 1985;Coombs et al 1989;Raible and Kruse 2000).…”

Section: Introductionmentioning

confidence: 99%

Bax, Bcl2, and p53 Differentially Regulate Neomycin- and Gentamicin-Induced Hair Cell Death in the Zebrafish Lateral Line

Coffin

Rubel

Raible

2013

JARO

102

116

View full text Add to dashboard Cite

Sensorineural hearing loss is a normal consequence of aging and results from a variety of extrinsic challenges such as excessive noise exposure and certain therapeutic drugs, including the aminoglycoside antibiotics. The proximal cause of hearing loss is often death of inner ear hair cells. The signaling pathways necessary for hair cell death are not fully understood and may be specific for each type of insult. In the lateral line, the closely related aminoglycoside antibiotics neomycin and gentamicin appear to kill hair cells by activating a partially overlapping suite of cell death pathways. The lateral line is a system of hair cell-containing sense organs found on the head and body of aquatic vertebrates. In the present study, we use a combination of pharmacologic and genetic manipulations to assess the contributions of p53, Bax, and Bcl2 in the death of zebrafish lateral line hair cells. Bax inhibition significantly protects hair cells from neomycin but not from gentamicin toxicity. Conversely, transgenic overexpression of Bcl2 attenuates hair cell death due to gentamicin but not neomycin, suggesting a complex interplay of pro-death and pro-survival proteins in drug-treated hair cells. p53 inhibition protects hair cells from damage due to either aminoglycoside, with more robust protection seen against gentamicin. Further experiments evaluating p53 suggest that inhibition of mitochondrial-specific p53 activity confers significant hair cell protection from either aminoglycoside. These results suggest a role for mitochondrial p53 activity in promoting hair cell death due to aminoglycosides, likely upstream of Bax and Bcl2.

show abstract

“…Recent studies from our laboratory and others have focused on aminoglycoside-induced hair cell death in the zebrafish (Williams and Holder 2000;Harris et al, 2003;Murakami et al, 2003;Ton and Parng 2005;Santos et al, 2006;Owens et al, 2007). The zebrafish offers several advantages to study mechanisms of hair cell toxicity.…”

Section: Introductionmentioning

confidence: 99%

Cisplatin-induced hair cell loss in zebrafish (Danio rerio) lateral line

Ou¹,

Raible²,

Rubel³

2007

Hearing Research

141

151

View full text Add to dashboard Cite

We have used time-lapse imaging to study cisplatin-induced hair cell death in lateral line neuromasts of zebrafish larvae in vivo. We found that cisplatin-induced hair cell death occurred much more slowly than had been shown to occur in aminoglycoside-induced hair cell death. By prelabeling hair cells with FM1-43FX, and assessing hair cell damage, it was established that cisplatin causes hair cell loss in the lateral line in a dose-dependent fashion. The kinetics of hair cell loss during exposure to different concentrations of cisplatin was also assessed and it was found that the onset of hair cell loss correlated with the accumulated dose of cisplatin. These data demonstrate the feasibility and repeatability of cisplatin damage protocols in the zebrafish lateral line and set the stage for future evaluations of modulation of cisplatin-induced hair cell death.

show abstract

The use of zebrafish for assessing ototoxic and otoprotective agents

Cited by 208 publications

References 80 publications

Hair Cell Toxicity in Anti-cancer Drugs: Evaluating an Anti-cancer Drug Library for Independent and Synergistic Toxic Effects on Hair Cells Using the Zebrafish Lateral Line

Hair Cell Toxicity in Anti-cancer Drugs: Evaluating an Anti-cancer Drug Library for Independent and Synergistic Toxic Effects on Hair Cells Using the Zebrafish Lateral Line

Bax, Bcl2, and p53 Differentially Regulate Neomycin- and Gentamicin-Induced Hair Cell Death in the Zebrafish Lateral Line

Cisplatin-induced hair cell loss in zebrafish (Danio rerio) lateral line

Contact Info

Product

Resources

About