Ototoxicity of Carboplatin in Guinea Pigs

Saito, Takehisa; Saitô, Hitoshi; Saito, Kenji; Wakui, Shinya; Manabe, Yasuhiro; Tsuda, Gota

doi:10.1016/s0385-8146(89)80003-3

Cited by 28 publications

(17 citation statements)

References 5 publications

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“…Similarly, equimolar concentrations of carboplatin have been found to be less toxic to auditory hair cells when compared with cisplatin. These observations also agree with clinical observations (Saito et al, 1989;Schweitzer et al, 1986;Taudy et al, 1992).…”

Section: Image Analysis Of Organ Of Corti Explants After Phalloidin±fsupporting

confidence: 92%

In Vitro Ototoxicity of aminoglycosides and platin derivatives. A semi-automatic assay for sensory hair cell damage in explanted rat organ of corti

Malgrange

Lefèbvre

Water

et al. 1998

Toxicology in Vitro

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AbstractÐThe ototoxic damage that drugs such as neomycin, kanamycin, colistin, cisplatin, transplatin and carboplatin cause on outer and inner hair cells in postnatal day 3 rat cochlear explants was investigated. Phalloidin±¯uorescein conjugate-stained stereocilia bundles of sensory hair cells were quanti®ed by video image analysis as a measurement of ototoxic eect. The video image quanti®cation system established dose±response curves for ototoxic drugs (e.g. calculation of an IC 50 ) and allowed comparisons between several ototoxins from the same family. This methodology provided the means to assess the ecacy of otoprotectant agents in preventing ototoxicity. Poly-l-aspartate (10 À5 M) and poly-l-glutamate (10 À5 M) protected auditory hair cells from neomycin (10 À3 M) toxicity while reduced glutathione (10 À3 M) provided protection against cisplatin (10 À4 M)-induced hair cell damage. # 1998 Published by Elsevier Science Ltd. All rights reserved Keywords: cochlea; aminoglycosides; cisplatin; ototoxicity; otoprotection.Abbreviations: DMEM = Dulbecco's modi®ed Eagle's medium; GSH = reduced glutathione; IHC = inner hair cells; OHC = outer hair cells; PBS = phosphate buered saline.

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Section: Image Analysis Of Organ Of Corti Explants After Phalloidin±fsupporting

confidence: 92%

In Vitro Ototoxicity of aminoglycosides and platin derivatives. A semi-automatic assay for sensory hair cell damage in explanted rat organ of corti

Malgrange

Lefèbvre

Water

et al. 1998

Toxicology in Vitro

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“…At higher doses of carboplatin, extensive loss of IHCs is exhibited across all cochlear turns and loss of OHCs is exhibited most prominently in the basal turn [17,18]. Studies of carboplatin administration in guinea pigs reveal that primarily OHCs are destroyed [19]. Given the potential for damage to cochlear structures, monitoring for carboplatin ototoxicity in pediatric cancer patients is a priority.…”

Section: Introductionmentioning

confidence: 99%

Monitoring carboplatin ototoxicity with distortion-product otoacoustic emissions in children with retinoblastoma

Bhagat

Bass

White

et al. 2010

International Journal of Pediatric Otorhinolaryngology

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Objective Carboplatin is a common chemotherapy agent with potential ototoxic side effects that is used to treat a variety of pediatric cancers, including retinoblastoma. Retinoblastoma is a malignant tumor of the retina that is usually diagnosed in young children. Distortion-product otoacoustic emission tests offer an effective method of monitoring for ototoxicity in young children. This study was designed to compare measurements of distortion-product otoacoustic emissions obtained before and after several courses of carboplatin chemotherapy in order to examine if (a) mean distortion-product otoacoustic emission levels were significantly different; and (b) if criterion reductions in distortion-product otoacoustic emission levels were observed in individual children. Methods A prospective repeated measures study. Ten children with a median age of 7.6 months (range, 3–72 months) diagnosed with unilateral or bilateral retinoblastoma were examined. Distortion-product otoacoustic emissions were acquired from both ears of the children with 65/55 dB SPL primary tones (f2= 793–7996 Hz) and a frequency resolution of 3 points/octave. Distortion-product otoacoustic emission levels in dB SPL were measured before chemotherapy treatment (baseline measurement) and after 3–4 courses of chemotherapy (interim measurement). Comparisons were made between baseline and interim distortion-product otoacoustic emission levels (collapsed across ears). Evidence of ototoxicity was based on criterion reductions (≥ 6 dB) in distortion-product otoacoustic emission levels. Results Significant differences between baseline and interim mean distortion-product otoacoustic emission levels were only observed at f2=7996 Hz. Four children exhibited criterion reductions in distortion-product otoacoustic emission levels. Conclusions Mean distortion-product otoacoustic emission levels at most frequencies were not changed following 3–4 courses of carboplatin chemotherapy in children with retinoblastoma. However, on an individual basis, children receiving higher doses of carboplatin exhibited criterion reductions in distortion-product otoacoustic emission level at several frequencies. These findings suggest that higher doses of carboplatin affect outer hair cell function, and distortion-product otoacoustic emission tests can provide useful information when monitoring children at risk of developing carboplatin ototoxicity.

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“…An unusual aspect of carboplatin is that its ototoxic effects ap pear to vary significantly across species. While carboplatin as well as other platinum analogs such as cisplatin typically damage the outer hair cells in many species, carboplatin selectively damages the inner hair cells in the chinchilla [2,5,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Early Damage in the Chinchilla Vestibular Sensory Epithelium from Carboplatin

1997

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Carboplatin, a second-generation platinum drug used in the treatment of cancer, can damage the hair cells in the vestibular system; however, little is known about the time course of its vestibulotoxic effects. The present study examined the acute vestibulotoxic effects of carboplatin (50 mg/kg) in the chinchilla. The duration of the nystagmus response evoked by cold caloric stimulation was significantly reduced 6 h following carboplatin treatment and showed a maximum, permanent reduction of approximately 50% by 24 h after injection. Light-microscopic observations at 6 h subsequent to injection revealed swollen afferent dendrites beneath type-I hair cells and the appearance of small vacuoles within the type-I hair cells; these changes were most pronounced in the crista ampullaris of the semicircular canals compared to the maculae of the utricle and saccule. Many mitochondria were swollen and partially depleted of their membranous infoldings. The mitochondrial abnormalities tended to be somewhat more severe in the hair cells than in their afferent terminals. The structural abnormalities in the mitochondria were more severe at 24 h following injection resulting in the appearance of larger and more numerous vacuoles in the hair cells. By 3 days after injection, many type-I hair cells were filled with large vacuoles which often caused severe distortion of the nucleus and disruption of the plasma membrane. Small vacuoles were occasionally observed in type-II hair cells, mainly in the crista ampullaris. These results indicate that the vestibulotoxic effects of carboplatin occur quite rapidly and cause significant disruption of the mitochondria in hair cells and their afferent terminals.

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Ototoxicity of Carboplatin in Guinea Pigs

Cited by 28 publications

References 5 publications

In Vitro Ototoxicity of aminoglycosides and platin derivatives. A semi-automatic assay for sensory hair cell damage in explanted rat organ of corti

In Vitro Ototoxicity of aminoglycosides and platin derivatives. A semi-automatic assay for sensory hair cell damage in explanted rat organ of corti

Monitoring carboplatin ototoxicity with distortion-product otoacoustic emissions in children with retinoblastoma

Early Damage in the Chinchilla Vestibular Sensory Epithelium from Carboplatin

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