Kanamycin and bumetanide ototoxicity: Anatomical, physiological and behavioral correlates

Santi, Peter A.; Nelson, David A.; Turner, Christopher W.

doi:10.1016/0378-5955(82)90040-5

Cited by 25 publications

(11 citation statements)

References 35 publications

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“…2) were within 5-8 dB of previously published results in untreated chinchillas using shock avoidance measures (Miller 1970;Blakeslee et al 1978;Salvi et al 1978;Santi et al 1982;Heffner and Heffner 1991;Lobarinas et al 2013) and 5-10 dB lower at frequencies 94 kHz relative to a food reinforced technique (Clark et al 1974).…”

Section: Thresholds In Quietsupporting

confidence: 76%

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss

Lobariñas

Salvi

Ding

2015

JARO

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Poorer hearing in the presence of background noise is a significant problem for the hearing impaired. Ototoxic drugs, ageing, and noise exposure can damage the sensory hair cells of the inner ear that are essential for normal hearing sensitivity. The relationship between outer hair cell (OHC) loss and progressively poorer hearing sensitivity in quiet or in competing background noise is supported by a number of human and animal studies. In contrast, the effect of moderate inner hair cell (IHC) loss or dysfunction shows almost no impact on behavioral measures of hearing sensitivity in quiet, when OHCs remain intact, but the relationship between selective IHC loss and hearing in noise remains relatively unknown. Here, a moderately high dose of carboplatin (75 mg/kg) that produced IHC loss in chinchillas ranging from 40 to 80 % had little effect on thresholds in quiet. However, when tested in the presence of competing broadband (BBN) or narrowband noise (NBN), thresholds increased significantly. IHC loss 960 % increased signal-to-noise ratios (SNRs) for tones (500-11,300 Hz) in competing BBN by 5-10 dB and broadened the masking function under NBN. These data suggest that IHC loss or dysfunction may play a significant role in listening in noise independent of OHC integrity and that these deficits may be present even when thresholds in quiet are within normal limits.

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Section: Thresholds In Quietsupporting

confidence: 76%

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss

Lobariñas

Salvi

Ding

2015

JARO

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“…Results of eighth nerve fiber recordings in animals that were chronically treated with aminoglycosides have shown that at least some remaining nerve fibers can be activated by sound but their functional properties are far from normal. (Kiang et al 1976;Dallos and Harris 1978;Schmiedt et al 1980;Santi et al 1982). The present results indicate that following a single local application of gentamicin, parts or even much of the cochlea can retain a normal appearance but the cytochemistry of the surviving cells can be changed to such a degree that normal function should not be assumed to be retained.…”

Section: Scope Of Gentamicin Effectsmentioning

confidence: 58%

Changes in Cytochemistry of Sensory and Nonsensory Cells in Gentamicin-Treated Cochleas

Imamura

Adams

2003

JARO - Journal of the Association for Research in Otolaryngolog

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Effects of a single local dose of gentamicin upon sensory and nonsensory cells throughout the cochlea were assessed by changes in immunostaining patterns for a broad array of functionally important proteins. Cytochemical changes in hair cells, spiral ganglion cells, and cells of the stria vascularis, spiral ligament, and spiral limbus were found beginning 4 days post administration. The extent of changes in immunostaining varied with survival time and with cell type and was not always commensurate with the degree to which individual cell types accumulated gentamicin. Outer hair cells, types I and II fibrocytes of the spiral ligament, and fibrocytes in the spiral limbus showed marked decreases in immunostaining for a number of constituents. In contrast, inner hair cells, type III fibrocytes and root cells of the spiral ligament, cells of the stria vascularis, and interdental cells in the spiral limbus showed less dramatic decreases, and in some cases they showed increases in immunostaining. Results indicate that, in addition to damaging sensory cells, local application of gentamicin results in widespread and disparate disruptions of a variety of cochlear cell types. Only in the case of ganglion cells was it apparent that the changes in nonsensory cells were secondary to loss or damage of hair cells. These results indicate that malfunction of the ear following gentamicin treatment is widespread and far more complex than simple loss of sensory elements. The results have implications for efforts directed toward detecting, preventing, and treating toxic effects of aminoglycosides upon the inner ear.

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“…Synergistic ototoxicity has been demonstrated previously between drugs such as loop diuretics and aminoglycosides (Santi et al 1982) as well as drugs and noise (Li and Steyger 2009). Anti-cancer drugs are a particularly fertile ground for studying synergistic effects because these drugs are in general used in combinations of two to four drugs, and almost by definition often have some degree of cytotoxicity.…”

Section: Combination Toxicity To Hair Cellsmentioning

confidence: 69%

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

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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.

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Kanamycin and bumetanide ototoxicity: Anatomical, physiological and behavioral correlates

Cited by 25 publications

References 35 publications

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss

Changes in Cytochemistry of Sensory and Nonsensory Cells in Gentamicin-Treated Cochleas

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

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