Otoprotective Effects of Fucoidan Reduce Cisplatin-Induced Ototoxicity in Mouse Cochlear UB/OC-2 Cells.

Cisplatin is a widely used standard chemotherapy for various cancers. However, cisplatin treatment is associated with severe ototoxicity. Fucoidan is a complex sulfated polysaccharide mainly derived from brown seaweeds, and it shows multiple bioactivities such as antimicrobial, anti-inflammatory, anticancer, and antioxidant activities. Despite evidence of the antioxidant effects of fucoidan, research on its otoprotective effects remains limited. Therefore, the present study investigated the otoprotective effects of fucoidan in vitro using the mouse cochlear cell line UB/OC-2 to develop new strategies to attenuate cisplatin-induced ototoxicity. We quantified the cell membrane potential and analyzed regulators and cascade proteins in the apoptotic pathway. Mouse cochlear UB/OC-2 cells were pre-treated with fucoidan before cisplatin exposure. The effects on cochlear hair cell viability, mitochondrial function, and apoptosis-related proteins were determined via flow cytometry, Western blot analysis, and fluorescence staining. Fucoidan treatment reduced cisplatin-induced intracellular reactive oxygen species production, stabilized mitochondrial membrane potential, inhibited mitochondrial dysfunction, and successfully protected hair cells from apoptosis. Furthermore, fucoidan exerted antioxidant effects against oxidative stress by regulating the Nrf2 pathway. Therefore, we suggest that fucoidan may represent a potential therapeutic agent for developing a new otoprotective strategy.

Otoprotective Effect of 2,3,4',5-Tetrahydroxystilbene-2-O-ß-d-Glucoside on Gentamicin-Induced Apoptosis in Mouse Cochlear UB/OC-2 Cells.

Excessive levels of reactive oxygen species (ROS) lead to mitochondrial damage and apoptotic cell death in gentamicin-induced ototoxicity. 2,3,4',5-Tetrahydroxystilbene-2-O-ß-d-glucoside (THSG), a bioactive constituent, isolated from Polygonum multiflorum Thunb., exhibits numerous biological benefits in treating aging-related diseases by suppressing oxidative damage. However, its protective effect on gentamicin-induced ototoxicity remains unexplored. Therefore, here, we aimed to investigate the otoprotective effect of THSG on gentamicin-induced apoptosis in mouse cochlear UB/OC-2 cells. We evaluated the effect of gentamicin and THSG on the ROS level, superoxide dismutase (SOD) activity, mitochondrial membrane potential, nuclear condensation, and lactate dehydrogenase (LDH) release, and the expression of apoptosis-related proteins was assessed to understand the molecular mechanisms underlying its preventive effects. The findings demonstrated that gentamicin increased ROS generation, LDH release, and promoted apoptotic cell death in UB/OC-2 cells. However, THSG treatment reversed these effects by suppressing ROS production and downregulating the mitochondrial-dependent apoptotic pathway. Additionally, it increased the SOD activity, decreased the expression of apoptosis-related proteins, alleviated the levels of the apoptotic cells, and impaired cytotoxicity. To the best of our knowledge, this is the first study to demonstrate that THSG could be a potential therapeutic option to attenuate gentamicin-induced ototoxicity.

Using multi-stimulus auditory steady state response to predict hearing thresholds in high-risk infants.

The purpose of this study was to investigate whether multi-stimulus auditory steady-state responses were capable of estimating hearing thresholds in high-risk infants. A retrospective chart review study. Three tertiary referral centers. Infants born between January 2004 and December 2006 who met the criteria for risk factors of congenital hearing loss were enrolled in the study. While under sedation, the multi-stimulus auditory steady-state response was used to determine multi-channel auditory steady-state response thresholds for high-risk infants younger than 13 months. Conditioned play audiometry was then applied to these children at 23-48 months of age to obtain pure tone audiograms. Auditory steady-state response thresholds and pure tone thresholds were then compared. A total of 249 high-risk infants were enrolled in the study. 39 infants were lost during follow-up. The remaining 216 infants completed both examinations. The Pearson correlation coefficients (r) between the ASSR levels and pure tone thresholds were 0.88, 0.94, 0.94 and 0.97 at 500, 1,000, 2,000 and 4,000 Hz, respectively. The strength of the relationship between the auditory steady-state responses and pure tone thresholds increased with more severe degrees of hearing loss and higher frequencies. We conclude that initial multichannel ASSR thresholds measured under sedation are highly correlated with pure tone thresholds obtained 2 or 3 years later. ASSR can be used to predict the frequency-specific hearing thresholds of high-risk infants and can provide information for early hearing intervention.

Cochlear implant mapping strategy to solve difficulty in speech recognition.

BACKGROUND: Cochlear implants (CIs) are viable treatment options in patients with severe to profound hearing loss. Speech recognition difficulties were reported in some CI recipients even with a good-aided hearing threshold. The aim of this study was to report a mapping strategy based on different target-aided hearing thresholds to achieve optimal speech recognition and maximize functional outcomes. The safety and efficacy of the mapping strategy were also inspected in the article. METHODS: This prospective repeated measures study enrolled 20 adult CI recipients with postlingual deafness using the MED-EL CI system. Word and sentence discrimination assessment and administration of a questionnaire pertaining to comfort level were conducted at the end of each session. The electrophysiological features of the CI mapping were recorded. RESULTS: The correlation between audiometry results and word and sentence recognition was not high. CIs performed best at an audiometry threshold between 25 and 35 dB. CONCLUSION: CI performance with the best perception relies on a balance between minimizing the hearing threshold and maximizing the dynamic range while maintaining an appropriate comfort level, which was achieved when the target hearing threshold was set at 25-35 dB in this study.

Bisdemethoxycurcumin-mediated Attenuation of Apoptosis Prevents Gentamicin-induced Ototoxicity in Mouse Cochlear UB/OC-2 Cells.

BACKGROUND/AIM: Gentamicin has been widely prescribed since the last two decades despite its ototoxicity and nephrotoxicity. Bisdemethoxycurcumin (BDMC) is an affordable and safe curcuminoid with medicinal properties. We aimed to understand the effects of BDMC on the gentamicin-induced hair cell damage in mouse cochlear UB/OC-2 cells, in order to elucidate the therapeutic potential of BDMC against gentamicin-induced ototoxicity. MATERIALS AND METHODS: We quantified the cell membrane potential and examined the regulators and cascade proteins in the intrinsic pathway of hair cell apoptosis. Mouse cochlear UB/OC-2 cells were treated with BDMC before exposure to gentamicin. The effects of BDMC on hair cell viability, mitochondrial function, and apoptosis-related proteins were examined by flow cytometry, western blot, and fluorescent staining. RESULTS: Our results revealed that BDMC reversed gentamicin-mediated cycle arrest at the G2/M phase, stabilizing the mitochondrial membrane potential, decreasing cleaved caspase proteins, and successfully reversing hair cell apoptosis. CONCLUSION: BDMC is a potential agent for reducing gentamicin-induced ototoxicity.

Ameliorative effect of taxifolin on gentamicin-induced ototoxicity via down-regulation of apoptotic pathways in mouse cochlear UB/OC-2 cells.

BACKGROUND: Taxifolin is a flavanonol with efficacious cytoprotective properties, such as anti-inflammatory, antioxidant, anticancer, hepatoprotective, and nephroprotective effects. However, the potential protective effects of taxifolin against gentamicin-induced ototoxicity have not been confirmed. In this study, the possible mechanisms underlying the effects of taxifolin on gentamicin-induced death of UB/OC-2 cochlear cells were investigated. METHODS: Mouse cochlear UB/OC-2 cells with or without taxifolin pretreatment were exposed to gentamicin, and the effects on cytotoxicity, reactive oxygen species (ROS) production, mitochondrial permeability transition, and apoptotic marker expression were examined using biochemical techniques, flow cytometry, western blotting, and fluorescent staining. RESULTS: Little or no apparent effect of taxifolin on cell viability was observed at concentrations less than 40 µM. Further investigations showed that gentamicin significantly inhibited cell viability in a concentration-dependent manner. Pretreatment with taxifolin attenuated gentamicin-induced lactate dehydrogenase release, as well as cellular cytotoxicity. In addition, taxifolin significantly prevented gentamicin-induced cell damage by decreasing ROS production, stabilizing mitochondrial membrane potential, and downregulating the mitochondrial pathway of apoptosis. CONCLUSION: In summary, pretreatment with taxifolin is effective for mitigating gentamicin-induced apoptotic cell death mediated by the mitochondrial pathway. Our data suggest that taxifolin provides a new approach to combat gentamicin-induced ototoxicity.

Comparison of intermittent intratympanic steroid injection and near-continual transtympanic steroid perfusion as salvage treatments for sudden sensorineural hearing loss.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate whether near-continual transtympanic steroid perfusion is more effective than intermittent intratympanic steroid injection as a salvage therapy for idiopathic sudden sensorineural hearing loss. STUDY DESIGN: Case control study. METHODS: We designed a case-control study consisting of 60 patients with sudden sensorineural hearing loss who did not respond well to systemic steroid therapy. From November 2008 to October 2010, we prospectively enrolled subjects for the transtympanic steroid perfusion therapy. We retrospectively collected data from age- and sex-matched patients who had undergone intratympanic steroid injection between January 2003 and October 2008. The audiological results of the two groups were compared. RESULTS: The presalvage pure tone threshold was 65.4 ± 13.5 dB in the transtympanic steroid perfusion group. After the therapy, the hearing threshold was improved by an average of 15.0 ± 9.7 dB, and 53.3% of subjects had improved by 10 dB or more. The speech discrimination score was improved from 12.6% ± 7.0% to 54.4 ± 6.4%. In the intratympanic steroid injection group, the presalvage pure tone threshold was 68.8 ± 16.0 dB. After the therapy, the hearing threshold was improved by an average of 10.7 ± 9.8 dB, and 43.3% of subjects had improved by 10 dB or more. The speech discrimination score was improved from 13.3 ± 6.0% to 46.4 ± 12%. The degree of hearing improvement was significantly greater in the transtympanic group. CONCLUSIONS: Both transtympanic steroid perfusion and intratympanic steroid injection can be used as salvage therapies for idiopathic sudden sensorineural hearing loss. Near-continual transtympanic steroid perfusions may provide better audiological results.

Intratympanic steroid injections as a salvage treatment for sudden sensorineural hearing loss: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The purpose of this study was to determine, through a randomized, double-blind, placebo-controlled trial, whether intratympanic steroid injections (ITSIs) could improve hearing recovery in patients with sudden sensorineural hearing loss (SSHL) who did not respond to initial systemic steroid therapy. STUDY DESIGN: This was a prospective, randomized, double-blind, placebo-controlled study. SETTING: The study was conducted in 2 tertiary referral centers. PATIENTS: A total of 60 patients with idiopathic SSHL who did not respond to an initial round of systemic steroid therapy were included in this study. The subjects were randomized into an ITSI group and an intratympanic normal saline injection (ITNI) group, which were matched by age and sex. A total of 55 subjects completed the study. INTERVENTION: Participants received either ITSIs or ITNIs. Both groups received 4 injections within a 2-week period. MAIN OUTCOME MEASURES: Pure-tone thresholds were compared between the 2 groups 1 month after injection therapy. RESULTS: In the ITNI group, the pure-tone threshold was 69.9 ± 18.5 dB before intratympanic injection therapy. After therapy, the hearing threshold improved by an average of 4.5 ± 6.5 dB, and 10.7% of subjects improved by 10 dB or more. In the ITSI group, the pure-tone threshold was 64.6 ± 17.7 dB before intratympanic injection therapy. After the therapy, the hearing threshold improved by an average of 9.8 ± 8.5 dB, and 44.4% of subjects improved by 10 dB or more. Both the response rate and the level of hearing improvement were significantly greater in the ITSI group than in the ITNI group. CONCLUSION: These results demonstrate that ITSIs are beneficial as a salvage therapy for the treatment of patients with idiopathic SSHL who fail to respond to initial systemic steroid therapy.