Ototoxicity: Of Mice and Men

Garetz, Susan L.; Schacht, Jochen

doi:10.1007/978-1-4612-4068-6_5

Cited by 26 publications

(20 citation statements)

References 187 publications

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“…Both drugs have ototoxic potential at high doses resulting in temporarily elevated thresholds and tinnitus. On cessation of aspirin/salicylate dosing, however, hearing returns to normal, and there is no confirmed report of any permanent auditory damage by salicylate (Garetz and Schacht, 1996). Consistent with the complete reversibility of salicylate ototoxicity, no hearing loss was measured in animals that received salicylate alone.…”

Section: Et Almentioning

confidence: 99%

Salicylate Protects Hearing and Kidney Function from Cisplatin Toxicity without Compromising its Oncolytic Action

Sha

Zotova

et al. 2002

Laboratory Investigation

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SUMMARY:Salicylate has recently been demonstrated to protect against the auditory and vestibular side effects of aminoglycoside antibiotics. Similarities in the toxic mechanisms suggest salicylate as a treatment strategy to prevent the ototoxic side effects of cisplatin (CDDP). We first tested protection of the inner ear in Wistar rats receiving a single infusion of 16 mg CDDP/kg body weight with or without treatment with 100 mg/kg salicylate (bid) for 5 days beginning one day before the CDDP infusion. Cisplatin induced a threshold shift of more than 30 dB (at 14 kHz; measured by auditory evoked brain stem response) that was significantly reduced by salicylate. We then examined the protective potential of salicylate on the cochlea, peripheral nerves, and kidney in a rat model of breast cancer-Fisher344 rats implanted with highly metastatic MTLn3 breast cancer cells. Animals received 3 ϫ 5 mg CDDP/kg (given every third day), and salicylate was administered at 100 mg/kg (bid) from 2 days before to 3 days after CDDP treatment. Salicylate significantly attenuated the CDDP-induced threshold shift from approximately 20 dB (at 16 and 24 kHz) to approximately 5 dB, and drastically reduced the loss of cochlear outer hair cells. Likewise, salicylate protected kidney function (measured as plasma blood urea nitrogen and creatinine levels) from CDDP toxicity. Protection of nerve conduction velocities of both sensory and motor nerves was minimal. The chemotherapeutic efficacy of CDDP on suppression of tumor mass and cancer cell metastasis remained unaffected by salicylate. The results suggest that administration of salicylate may become the basis of an effective therapeutic intervention against the ototoxic and nephrotoxic side effects associated with CDDP chemotherapy. (Lab Invest 2002, 82:585-596).

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Section: Et Almentioning

confidence: 99%

Salicylate Protects Hearing and Kidney Function from Cisplatin Toxicity without Compromising its Oncolytic Action

Sha

Zotova

et al. 2002

Laboratory Investigation

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“…Karlsen and Sand (1987) reported that CoCl 2 treatment affected the mechanosensitivity of the lateral line in the roach (Rutilus rutilus) without affecting microphonic activity from the utricle. Streptomycin, when administered systemically or directly into the inner ear, is vestibulotoxic and cochleotoxic in mammals (reviews: Garetz and Schacht 1996;Bagger-Sjoback 1997). This aminoglycoside also blocks transduction channels in saccular hair cells in adult bullfrogs (Kroese et al 1989).…”

Section: Inner Ear Function and Behavioral Responsesmentioning

confidence: 99%

Lateral line-mediated rheotactic behavior in tadpoles of the African clawed frog (Xenopus laevis)

2004

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Tadpoles (Xenopus laevis) have a lateral line system whose anatomical structure has been described, but whose functional significance has not been closely examined. These experiments tested the hypothesis that the lateral line system is involved in rheotaxis. Tadpoles in developmental stages 47-56 oriented toward the source of a water current. Orientation was less precise after treatment with cobalt chloride or streptomycin, but was similar to that of untreated animals after exposure to gentamicin. In no current conditions, tadpoles exhibited a characteristic head-down posture by which they held themselves in the water column at an angle around 45°. This body posture became significantly less tilted in the presence of water current. Treatment with cobalt chloride or streptomycin increased the angle of tilt close to that seen in no current conditions, while gentamicin treatment tended to decrease tilt angle. The data are consistent with anatomical and physiological findings that tadpole neuromasts are similar to superficial, but not canal, neuromasts in fishes, and they suggest that the lateral line system is involved in both directional current detection and currentrelated postural adjustments in Xenopus.

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“…Muitos estudos clínicos dos efeitos da amicacina no homem têm revelado que a mesma pode produzir alterações que provocam zumbidos, perda auditiva nas freqüências altas e, mais raramente, distúrbios vestibulares 18 . Uma das limitações mais sérias na aplicação terapêutica desta droga é a ototoxicidade induzida que provoca lesões permanentes no sistema coclear e vestibular 6 . A amicacina em dose de 400mg/kg/dia intramuscular provoca completa eliminação das células ciliadas externas e lesão parcial das internas, na primeira e na segunda espira da cóclea de cobaias, com lesões menos intensas na terceira e quarta espiras, ocorrendo lesões parciais nas células ciliadas internas 8 .…”

Section: Resumo / Summaryunclassified