Early Physiological and Cellular Indicators of Cisplatin-Induced Ototoxicity

Chen, Yingying; Bielefeld, Eric C.; Mellott, Jeffrey G.; Wang, Weijie; Mafi, Amir M.; Yamoah, Ebenezer N.; Bao, Jianxin

doi:10.1007/s10162-020-00782-z

Cited by 14 publications

(9 citation statements)

References 67 publications

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“…The mechanisms of cisplatin-induced cochlear dysfunction are associated with cellular damage as well as disruption of cochlear homeostasis. After cisplatin administration, cellular degeneration was observed in outer hair cells of the organ of Corti, marginal cells of the stria vascularis, spiral ganglion cells, and synaptopathy between inner hair cells and spiral ganglion neurons ( Brock et al, 2012 ; Chen et al, 2021 ).…”

Section: Preclinical Data Of Cisplatin Ototoxicitymentioning

confidence: 99%

Preferential Cochleotoxicity of Cisplatin

et al. 2021

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Cisplatin-induced ototoxicity in humans is more predominant in the cochlea than in the vestibule. Neither definite nor substantial vestibular dysfunction after cisplatin treatment has been consistently reported in the current literature. Inner ear hair cells seem to have intrinsic characteristics that make them susceptible to direct exposure to cisplatin. The existing literature suggests, however, that cisplatin might have different patterns of drug trafficking across the blood-labyrinth-barrier, or different degrees of cisplatin uptake to the hair cells in the cochlear and vestibular compartments. This review proposes an explanation for the preferential cochleotoxicity of cisplatin based on current evidence as well as the anatomy and physiology of the inner ear. The endocochlear potential, generated by the stria vascularis, acting as the driving force for hair cell mechanoelectrical transduction might also augment cisplatin entry into cochlear hair cells. Better understanding of the stria vascularis might shed new light on cochleotoxic mechanisms and inform the development of otoprotective interventions to moderate cisplatin associated ototoxicity.

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Section: Preclinical Data Of Cisplatin Ototoxicitymentioning

confidence: 99%

Preferential Cochleotoxicity of Cisplatin

et al. 2021

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“…Time sequence studies [44,45] exploring impairment processes at these 3 sites have verified that they run in parallel, other than secondary injuries dependent on another ototoxic process. A recent study found that a delay in ABR wave 1 latency which probably implied the damage to SGN mitochondria and myelination was the earliest functional and cellular changes after cisplatin treatment, indicating SGN as an early and direct damaging target in cisplatin-induced ototoxicity [46]. In the present study, the damaging target was determined by the analysis of histological and immunohistochemical staining of the basilar membrane and mid-modiolar sections.…”

Section: Discussionmentioning

confidence: 57%

An enhanced antioxidant strategy of astaxanthin encapsulated in ROS-responsive nanoparticles for combating cisplatin-induced ototoxicity

Wang

Chen

et al. 2022

J Nanobiotechnol

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Background Excessive accumulation of reactive oxygen species (ROS) has been documented as the crucial cellular mechanism of cisplatin-induced ototoxicity. However, numerous antioxidants have failed in clinical studies partly due to inefficient drug delivery to the cochlea. A drug delivery system is an attractive strategy to overcome this drawback. Methods and results In the present study, we proposed the combination of antioxidant astaxanthin (ATX) and ROS-responsive/consuming nanoparticles (PPS-NP) to combat cisplatin-induced ototoxicity. ATX-PPS-NP were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units, which scavenged ROS and disintegrate to release the encapsulated ATX. The ROS-sensitivity was confirmed by 1H nuclear magnetic resonance spectroscopy, transmission electron microscopy and an H2O2 ON/OFF stimulated model. Enhanced release profiles stimulated by H2O2 were verified in artificial perilymph, the HEI-OC1 cell line and guinea pigs. In addition, ATX-PPS-NP efficiently inhibited cisplatin-induced HEI-OC1 cell cytotoxicity and apoptosis compared with ATX or PPS-NP alone, suggesting an enhanced effect of the combination of the natural active compound ATX and ROS-consuming PPS-NP. Moreover, ATX-PPS-NP attenuated outer hair cell losses in cultured organ of Corti. In guinea pigs, NiRe-PPS-NP verified a quick penetration across the round window membrane and ATX-PPS-NP showed protective effect on spiral ganglion neurons, which further attenuated cisplatin-induced moderate hearing loss. Further studies revealed that the protective mechanisms involved decreasing excessive ROS generation, reducing inflammatory chemokine (interleukin-6) release, increasing antioxidant glutathione expression and inhibiting the mitochondrial apoptotic pathway. Conclusions Thus, this ROS-responsive nanoparticle encapsulating ATX has favorable potential in the prevention of cisplatin-induced hearing loss. Graphical Abstract

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“…However, it would be better to validate by other models of hearing loss. For example, we have found that early hearing loss in cisplatin-induced hearing is associated with mitochondrial loss in SGNs only ( Chen et al, 2021 ), and it would be interesting to apply the same method to identify curvature profiles in this model. In addition, most of noise-induced hearing loss in humans is less likely to cause purely syanptopathy, and may include other cochlear damages such as loss of OHCs (e.g., Fernandez et al, 2020 ); noise exposure can also create early damage to the extreme base of the cochlea which may influence mass-stiffness properties of the basilar membrane.…”

Section: Discussionmentioning

confidence: 99%

Detecting Cochlear Synaptopathy Through Curvature Quantification of the Auditory Brainstem Response

Bao

Jegede

Hawks³

et al. 2022

Front. Cell. Neurosci.

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The sound-evoked electrical compound potential known as auditory brainstem response (ABR) represents the firing of a heterogenous population of auditory neurons in response to sound stimuli, and is often used for clinical diagnosis based on wave amplitude and latency. However, recent ABR applications to detect human cochlear synaptopathy have led to inconsistent results, mainly due to the high variability of ABR wave-1 amplitude. Here, rather than focusing on the amplitude of ABR wave 1, we evaluated the use of ABR wave curvature to detect cochlear synaptic loss. We first compared four curvature quantification methods using simulated ABR waves, and identified that the cubic spline method using five data points produced the most accurate quantification. We next evaluated this quantification method with ABR data from an established mouse model with cochlear synaptopathy. The data clearly demonstrated that curvature measurement is more sensitive and consistent in identifying cochlear synaptic loss in mice compared to the amplitude and latency measurements. We further tested this curvature method in a different mouse model presenting with otitis media. The change in curvature profile due to middle ear infection in otitis media is different from the profile of mice with cochlear synaptopathy. Thus, our study suggests that curvature quantification can be used to address the current ABR variability issue, and may lead to additional applications in the clinic diagnosis of hearing disorders.

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Early Physiological and Cellular Indicators of Cisplatin-Induced Ototoxicity

Cited by 14 publications

References 67 publications

Preferential Cochleotoxicity of Cisplatin

Preferential Cochleotoxicity of Cisplatin

An enhanced antioxidant strategy of astaxanthin encapsulated in ROS-responsive nanoparticles for combating cisplatin-induced ototoxicity

Detecting Cochlear Synaptopathy Through Curvature Quantification of the Auditory Brainstem Response

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