Cisplatin ototoxicity in guinea pigs with special reference to toxic effects in the stria vascularis

Kohn, Sarah; Fradis, Milo; Pratt, Hillel; Zidan, Jamal; Podoshin, L; Robinson, Eliezer; Nir, Izhak

doi:10.1288/00005537-198808000-00015

Cited by 66 publications

(28 citation statements)

References 19 publications

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“…Morphologically, edema formation in the SV appeared during the early phase of degeneration after CDDP treatment, followed by severe atrophy during the late phase. The time course of morphological changes of the SV observed in this study was similar to that observed in previous studies using systemic CDDP application [3][4][5]. TUNEL assays revealed induction of apoptotic cell death in the SV after CDDP treatment.…”

Section: Cell Death Model For the Svsupporting

confidence: 88%

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Mechanisms of Apoptosis Induced by Cisplatin in Marginal Cells in Mouse Stria Vascularis

Lee

Nakagawa²,

Kita

et al. 2004

ORL

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Degeneration of the stria vascularis (SV) is amongst the major causes of cisplatin (CDDP)-induced hearing impairment. The pathways of apoptosis occurring in the SV due to CDDP were examined using a mouse experimental model. Temporal bones of adult C57BL/6 mice were collected on days 3, 7 and 14 after the local application of CDDP. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and immunostaining for apoptosis-related proteins or reactive radical species were employed for analysis. Local application of CDDP caused apoptotic cell death of marginal cells 3 days after CDDP treatment. Immunohistochemical analyses demonstrated activation of caspase-3 and -9, but not -8, and redistribution of cytochrome c in affected marginal cells, indicating a caspase-dependent, mitochondrion-mediated apoptotic pathway in marginal cells. Temporary expression of hydroxynonenal, nitrotyrosine and inducible nitric oxide synthase in the SV was observed at the induction of apoptosis in marginal cells. CDDP toxicity generates reactive radical species in the SV, which causes mitochondrial membrane permeabilization leading to apoptosis of marginal cells.

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Section: Cell Death Model For the Svsupporting

confidence: 88%

“…The stria vascularis (SV) is known as a primary site of CDDP ototoxicity. In the SV, it has been shown that marginal cells are especially vulnerable to CDDP-induced damage [3,4]. In addition, it has been demonstrated that there is a high correlation between marginal cell damage and hearing loss [5].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Apoptosis Induced by Cisplatin in Marginal Cells in Mouse Stria Vascularis

Lee

Nakagawa²,

Kita

et al. 2004

ORL

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“…Despite the many beneficial features of cisplatin, serious side effects are nephrotoxicity, neurotoxicity, and ototoxicity. In regard to ototoxicity, it is believed that cisplatin selectively damages the outer hair cells within the organ of Corti, spiral ganglion cells and cells within the stria vascularis [2,3]. Ototoxicity can occur anytime from hours to days after treatment.…”

Section: Introductionmentioning

confidence: 99%

Incidence of Cisplatin Induced Ototoxicity in Adults with Head and Neck Cancer

Greene

Standring

Siddiqui

et al. 2015

Advances in Otolaryngology

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Objective. To elucidate the incidence of cisplatin induced ototoxicity in adult patients, with a focus on an adult population. Study Design. IRB approved retrospective study. Methods. The charts of patients who underwent cisplatin therapy from 1995 to present were reviewed. Inclusion criteria were (1) cisplatin as the primary chemotherapeutic agent and (2) hearing evaluation performed prior to and after treatment. Audiometric thresholds were measured by presenting pure-tone stimuli at 0.25 to 10.0 kHz. Criteria for hearing loss were based on the Chang criteria. Cochlear radiation doses were also calculated in patients with primary tumors in their head and neck or brain. Results. There were 1565 patients that had undergone therapy with cisplatin from 1995 to 2014, which 30 met inclusion criteria. Eight were patients treated for head and neck or brain cancer. Evaluation with ANOVA testing identified statistically significant decline in audiometric scores for WRS and pure tone frequencies 500, 2000, 4000, 6000, and 8000 Hz in the right ear. Overall, hearing loss was noted with 63% incidence and in patients who received radiation to their cochlea and cisplatin. Conclusion. The incidence of cisplatin induced ototoxicity was significant and even more prevalent in those patients receiving both cisplatin and radiation to their cochlea.

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“…Although cisplatin is one of the most potent OHC toxins known [Anniko and Sobin, 1986], it may also cause hearing loss by affecting other inner ear structures, such as the stria vascularis [Nakai et al, 1982;Tange and Vuzevski, 1984;Kohn et al, 1988;Saito and Aran, 1994;Watanabe et al, 2002]. Indeed, a major decrease in the endocochlear potential (EP), implying stria vascularis dysfunction, has been observed early after the occurrence of cisplatin-induced threshold shifts [Klis et al, 2000[Klis et al, , 2002Tsukasaki et al, 2000].…”

Section: Introductionmentioning

confidence: 99%

Cisplatin Ototoxicity Involves Organ of Corti, Stria Vascularis and Spiral Ganglion: Modulation by αMSH and ORG 2766

et al. 2003

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It has been shown that αMSH and the nonmelanotropic ACTH/MSH(4–9) analog ORG 2766 can ameliorate cisplatin-induced neurotoxicity and ototoxicity. Here, we investigated whether these peptides delay the occurrence of the cisplatin-induced shift in auditory threshold, and whether they affect the subsequent recovery of cochlear potentials. Chronically implanted round window electrodes were used to obtain daily recordings of auditory nerve compound action potentials (CAP) and cochlear microphonics at frequencies ranging from 2 to 16 kHz. Cisplatin (1.5 mg/kg i.p.) plus αMSH, ORG 2766 (75 µg/kg s.c.), or saline were injected daily until the 40-dB CAP threshold shift at 8 kHz was reached. Endocochlear potential (EP) was measured either 1–2 days or 28 days later, followed by morphometric analysis of the cochlea. Peptide cotreatment did not consistently delay the threshold shift; however, the CAP threshold recovered faster and to a greater extent, with the potency order being αMSH > ORG 2766 > saline. Significant recovery at the 2 highest frequencies was seen in the αMSH-treated animals only. CAP amplitude at high sound pressures, which depends more on nerve function than on outer hair cell (OHC) function, decreased severely in all groups but recovered significantly in the αMSH- and completely in the ORG-2766-cotreated group. EP was significantly lower in the first days after the threshold shift but had completely recovered at 28 days. Morphometric analysis of the spiral ganglion also indicated involvement of ganglion cells. OHC loss was most severe in the basal turn of saline-cotreated animals. These data suggest that the cisplatin-induced acute threshold shift might be due to reversible strial failure, whereas subsequent OHC survival determines the final degree of functional recovery. Both OHC loss and neuronal function were ameliorated by peptide cotreatment.

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Cisplatin ototoxicity in guinea pigs with special reference to toxic effects in the stria vascularis

Cited by 66 publications

References 19 publications

Mechanisms of Apoptosis Induced by Cisplatin in Marginal Cells in Mouse Stria Vascularis

Mechanisms of Apoptosis Induced by Cisplatin in Marginal Cells in Mouse Stria Vascularis

Incidence of Cisplatin Induced Ototoxicity in Adults with Head and Neck Cancer

Cisplatin Ototoxicity Involves Organ of Corti, Stria Vascularis and Spiral Ganglion: Modulation by αMSH and ORG 2766

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