Gentamicin‐Induced Hair Cell Death Is Not Dependent on the Apoptosis Receptor Fas

Bodmer, Daniel; Brors, Dominik; Pak, Kwang; Bodmer, Morana; Ryan, Allen F.

doi:10.1097/00005537-200303000-00012

Cited by 21 publications

(19 citation statements)

References 24 publications

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“…54 A previous study shows GM not causing apoptosis through extrinsic apoptotic pathways via Fas receptors; 55 much evidence indicates mitochondrial-dependent intrinsic apoptotic pathways' role in aminoglycoside-induced cell apoptosis. Genetic and biochemical evidence also portends mitochondrial dysfunction as crucial in susceptibility to aminoglycoside ototoxicity.…”

Section: Discussionmentioning

confidence: 99%

Transient ischemia/hypoxia enhances gentamicin ototoxicity via caspase-dependent cell death pathway

Kao

Tsai

Lai

et al. 2011

Laboratory Investigation

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Aminoglycoside ototoxicity is a common cause of drug-induced hearing loss. Toxicity is dose related, but some patients may still develop hearing loss even under safe dosage. Apart for genetic idiosyncrasy, indirect evidences imply that ischemia may increase the aminoglycoside ototoxic sensitivity because common clinical situations associated with cochlear ischemia such as noise, sepsis, and shock are known to augment the development of aminoglycoside ototoxicity. At present, a direct interaction of cochlear ischemia and aminoglycoside ototoxicity is still lacking. This study demonstrated a direct evidence of increased gentamicin (GM) ototoxic sensitivity in chronic guinea pig models of transient cochlear ischemia. No permanent auditory changes were observed after a single dose of GM (125 mg/kg) or after transient cochlear ischemia for 30 min. Persistent and significant auditory threshold shift was detected when GM was given after transient cochlear ischemia. Cochlear hair cells and spiral ganglion neurons are the major regions affected. Apoptosis contributes to hair cell death during acute interaction of ischemia and GM ototoxicity. Increased apoptotic cell death was also depicted when GM crossreacted with hypoxia in vitro, using cochlear cell lines. Generation of reactive oxygen species, loss of mitochondrial membrane potential, calcium release, and caspase-dependent apoptotic cell death were shown during the interaction of hypoxia and GM ototoxicity in vitro. This synergistic ototoxicity may be critical to aminoglycoside-induced hearing loss in clinical scenarios. The results should improve our understanding of the interacting mechanism and potential preventive strategy to aminoglycoside ototoxicity.

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Section: Discussionmentioning

confidence: 99%

Transient ischemia/hypoxia enhances gentamicin ototoxicity via caspase-dependent cell death pathway

Kao

Tsai

Lai

et al. 2011

Laboratory Investigation

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“…In order to preserve the residual hearing, atraumatic implant electrodes have been developed in order to minimise inner ear trauma. In addition, inner ear hair cell protecting agents such as steroids are used in conjunction with atraumatic implant surgical techniques to maximise preservation of residual hearing [Bodmer et al, 2003]. Pilot studies using hearing preserving cochlear implants in adult patients with gentamicin-induced ototoxicity or congenital partial deafness have shown excellent outcomes and hearing preservation rates [Skarzynski et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

A Case Series of Paediatric Hearing Preservation Cochlear Implantation: A New Treatment Modality for Children with Drug-Induced or Congenital Partial Deafness

Kuthubutheen¹,

Hedne²,

Krishnaswamy

et al. 2012

Audiol Neurotol

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Objective: To investigate the use of hearing preservation cochlear implantation in children with partial deafness. Patients and Methods: Five children with either drug-induced or congenital partial deafness were enrolled in a pilot study. The patients ranged in age from 13 months to 14 years. Implantation was performed using a hearing preservation technique. A Flex EAS electrode (MED-EL, Innsbruck, Austria) was used in all full insertions. Results: Low frequency hearing was preserved in all patients with postoperative bone conduction within 10 dB of the preoperative hearing levels. These changes were preserved over the follow-up period of 12 months. There were significant improvements in speech perception. Conclusion: Hearing preservation cochlear implantation is a new effective modality in children with partial deafness.

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“…Each acquisition field contained approximately 15 IHCs and 60 OHCs. Disorganization of stereocilia is an early sign of HC pathology, and phalloidin-labelled HCs reflect the number of living HCs [Kopke et al, 1997;Bodmer et al, 2003]. HCs with a regular phalloidin-labelled hair bundle were considered undamaged or normal.…”

Section: Evaluation Of the Toxicity Of Ply On Cochlear Hair Cells In mentioning

confidence: 99%

Zinc Protection against Pneumolysin Toxicity on Rat Cochlear Hair Cells

Franco-Vidal¹,

Beurg²,

Darrouzet³

et al. 2007

Audiol Neurotol

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Streptococcus pneumoniae can induce local and systemic diseases such as meningitis, otitis media, and pneumonia. One third of these meningitis cases can be associated with irreversible sensorineural hearing loss whose mechanisms likely involves the exotoxin pneumolysin (PLY) that irreversibly damages cochlear hair cells (HCs). In the respiratory system and in neuron it has been demonstrated that zinc deficiency increases severity and mortality of such infections in animal models and in children. Moreover, zinc supplementation can decrease the severity of pneumococcal respiratory infections. The aim of our study was to assess the potential protective effect of zinc against PLY toxicity on HCs in culture. Our results showed that in the presence of zinc at concentration as low as 1 µM, the toxicity of PLY was largely reduced by about 50% for both inner and outer HCs. At 300 µM of zinc, protection significantly increased with 62 and 55.2% for IHCs and OHCs, respectively. Our results suggest that the protective effect of zinc is likely due to an inhibition of the toxin incorporation and aggregation into the plasma membrane, thus preventing calcium influx through the toxin pores. Our findings raise the possibility that treatments with zinc may help to prevent debilitating otological sequelae from pneumococcal infection.

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Gentamicin‐Induced Hair Cell Death Is Not Dependent on the Apoptosis Receptor Fas

Abstract: The gentamicin-mediated hair cell death is not dependent on a functional Fas receptor.

Cited by 21 publications

References 24 publications

Transient ischemia/hypoxia enhances gentamicin ototoxicity via caspase-dependent cell death pathway

Transient ischemia/hypoxia enhances gentamicin ototoxicity via caspase-dependent cell death pathway

A Case Series of Paediatric Hearing Preservation Cochlear Implantation: A New Treatment Modality for Children with Drug-Induced or Congenital Partial Deafness

Zinc Protection against Pneumolysin Toxicity on Rat Cochlear Hair Cells

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