scholarly journals Protective effect of ethosuximide on hearing in NOD/LtJ mice via blockage of endogenous apoptosis

2020 ◽  
Vol 19 (2) ◽  
pp. 299-304
Author(s):  
Dejun Zhang ◽  
Guofang Guan ◽  
Yingyuan Guo ◽  
Yanru Hao ◽  
Fang Guo ◽  
...  

Purpose: To determine the protective effect of ethosuximide on the hearing of NOD/LtJ mice, and the underlying mechanism of action. Methods: The mice were randomly assigned to control and treatment groups (20 mice per group). Mice in the treatment group were administered ethosuximide intraperitoneally at a dose of 200mg/kg body weight (bwt), while those in the control group received an equivalent dose of saline via the same route. Both groups were subjected to auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) tests, as well as determination of mRNA expressions of α1G, α1H, α1I, m-calpain, μ-calpain, and caspase-3. Results: At ages of 6 and 9 weeks, ABR values were significantly lower in the treatment group than those in the control group (p < 0.05). At age 3, 6 and 9 weeks, control group DPOAE values were much lower than those in the treatment group. However, at signal frequency of 35344 Hz, DPOAE value was significantly reduced in the treatment group (p < 0.05). There was significant down-regulation in mRNA expressions of α1G, α1H, α1I, m-calpain, μ-calpain and caspase-3, in the treatment group, when compared with the control group (p < 0.05). Conclusion: Ethosuximide delays mice hearing loss and protects their hearing via a mechanism involving blockage of endogenous apoptotic pathways. This mechanism may provide guidance in the search for suitable new drugs. Keywords: Ethosuximide, Endogenous apoptosis, Hearing, Protection

2012 ◽  
Vol 126 (5) ◽  
pp. 464-469 ◽  
Author(s):  
S Alıcura Tokgöz ◽  
E Vuralkan ◽  
N D Sonbay ◽  
M Çalişkan ◽  
C Saka ◽  
...  

AbstractObjective:This experimental study aimed to investigate the effects of vitamins E, B and C and l-carnitine in preventing cisplatin-induced ototoxicity.Methods:Twenty-five adult, male, Wistar albino rats were randomly allocated to receive intraperitoneal cisplatin either alone or preceded by vitamins B, E or C or l-carnitine. Auditory brainstem response (i.e. hearing thresholds and wave I–IV intervals) and distortion product otoacoustic emissions (i.e. signal-to-noise ratios) were recorded before and 72 hours after cisplatin administration.Results:The following statistically significant differences were seen: control group pre- vs post-treatment wave I–IV interval values (p < 0.05); control vs vitamin E and B groups' I–IV interval values (p < 0.05); control vs other groups' hearing thresholds; vitamin E vs vitamin B and C and l-carnitine groups' hearing thresholds (p < 0.05); and vitamin B vs vitamin C and l-carnitine groups' hearing thresholds (p < 0.05). Statistically significant decreases were seen when comparing the initial and final signal-to-noise ratios in the control, vitamin B and l-carnitine groups (2000 and 3000 Hz; p < 0.01), and the initial and final signal-to-noise ratios in the control group (at 4000 Hz; p < 0.01).Conclusion:Vitamins B, E and C and l-carnitine appear to reduce cisplatin-induced ototoxicity in rats. The use of such additional treatments to decrease cisplatin-induced ototoxicity in humans is still under discussion.


1994 ◽  
Vol 110 (1) ◽  
pp. 22-38 ◽  
Author(s):  
James W. Hall ◽  
Jane E. Baer ◽  
Patricia A. Chase ◽  
Mitchell K. Schwaber

Three electrophysiologic audiologic procedures-aural immittance measurement, auditory brainstem response (ABR), and otoacoustic emissions (OAE) — were first described in the 1970's. Immittance measurement and ABR have contributed importantly for years to the assessment of auditory function in children and adults, whereas OAEs have not yet been incorporated into the everyday audiology test battery. In this article, we argue that the transition from OAE measurement by hearing scientists in laboratory settings to routine application by audiologists in the clinic will be greatly facilitated by (1) comprehensive, large-scale studies of the effects of subject characteristics, such as gender and age (from infancy to advancing adulthood), on both transient evoked (TEOAE) and distortion product (DPOAE) otoacoustic emissions; (2) clinical investigations of TEOAE and DPOAE in sizeable patient populations with specific neurotologic diagnoses; (3) guidelines for OAE test protocols in clinical environments; and (4) clear criteria for OAE analysis in clinical populations.


2020 ◽  
Vol 21 (10) ◽  
pp. 3503 ◽  
Author(s):  
Chang Ho Lee ◽  
Da-hye Lee ◽  
So Min Lee ◽  
So Young Kim

Previous studies have described the effects of zingerone (ZO) on cisplatin (CXP)-induced injury to the kidneys, liver, and other organs but not to the cochlea. This study aimed to investigate the effects of ZO on CXP-induced ototoxicity. Eight-week-old Sprague–Dawley rats were used and divided into a control group, a CXP group, and a CXP + ZO group. Rats in the CXP group received 5 mg/kg/day CXP intraperitoneally for five days. Rats in the CXP + ZO group received 5 mg/kg/day CXP intraperitoneally for five days and 50 mg/kg/day ZO intraperitoneally for seven days. Auditory brainstem response thresholds (ABRTs) were measured before (day 0) and after (day 10) drug administration. Cochlear histology was examined using hematoxylin and eosin (H&E) staining and cochlear whole mounts. The expression levels of cytochrome P450 (CYP)1A1, CYP1B1, inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NFκB), tumor necrosis factor alpha (TNFα), and interleukin 6 (IL6) were estimated using quantitative reverse transcription-polymerase chain reaction. The expression levels of heme oxygenase 1 (HO1) and caspase 3 were analyzed via Western blotting. The auditory thresholds at 4, 8, and 16 kHz were attenuated in the CXP + ZO group compared with the CXP group. The mRNA expression levels of CYP1A1, CYP1B1, iNOS, NFκB, TNFα, and IL6 were lower in the CXP + ZO group than in the CXP group. The protein expression levels of HO1 and caspase 3 were lower in the CXP + ZO group than in the CXP group. Cotreatment with ZO exerted otoprotective effects against CXP-induced cochlear injury via antioxidative and anti-inflammatory activities involving CYPs, iNOS, NFκB, and TNFα.


2021 ◽  
Vol 35 ◽  
pp. 205873842110340
Author(s):  
Jie Wang ◽  
Ke-yong Tian ◽  
Ying Fang ◽  
Hui-min Chang ◽  
Ya-nan Han ◽  
...  

Introduction Cruciferous vegetables are a rich source of sulforaphane (SFN), which acts as a natural HDAC inhibitor (HDACi). Our previous study found that HDACi could restore histone acetyltransferase/histone deacetylase (HAT/HDAC) balance in the cochlea and attenuate gentamicin-induced hearing loss in guinea pigs. Here, we investigated the protective effect of SFN on cisplatin-induced hearing loss (CIHL). Methods Thirty rats were randomly divided into 3 equal groups: the control group, cisplatin group, and SFN+cisplatin group. Rats were injected with SFN (30 mg/kg once a day) and cisplatin (7 mg/kg twice a day) for 7 days to investigate the protective role of SFN on CIHL. We observed auditory brainstem response (ABR) threshold shifts and immunostained cochlear basilar membranes of rats. For in vitro experiments, we treated HEI-OC1 cells and rat cochlear organotypic cultures with SFN (5, 10, and 15 μM) and cisplatin (10 μM). Immunofluorescence, cell viability, and protein analysis were performed to further analyze the protective mechanism of SFN on CIHL. Results SFN (30 mg/kg once a day) decreased cisplatin (7 mg/kg twice a day)-induced ABR threshold shifts and outer hair cell loss. CCK-8 assay showed that cisplatin (10 μM) reduced the viability of HEI-OC1 cells to 42%, and SFN had a dose-dependent protective effect. In cochlear organotypic cultures, we found that SFN (10 and 15 μM) increased cisplatin (10 μM)-induced myosin 7a+ cell count and restored ciliary morphology. SFN (5, 10, and 15 μM) reversed the cisplatin (10 μM)-induced increase in HDAC2, -4, and -5 and SFN (15 μM) reversed the cisplatin (10 μM)-induced decrease in H3-Ack9 [acetyl-histone H3 (Lys9)] protein expression in HEI-OC1 cells. Neither cisplatin nor cisplatin combined with SFN affected the expression of HDAC7, or HDAC9. Conclusion SFN prevented disruption of the HAT/HDAC balance, protecting against CIHL in rats.


2019 ◽  
Author(s):  
Naomi Bramhall ◽  
Garnett McMillan ◽  
Frederick Gallun ◽  
Dawn Konrad-Martin

Tinnitus is one of the predicted perceptual consequences of cochlear synaptopathy, a type of age-, noise-, or drug-induced auditory damage that has been demonstrated in animal models to cause homeostatic changes in central auditory gain. Although synaptopathy has been observed in human temporal bones, assessment of this condition in living humans is limited to indirect non-invasive measures such as the auditory brainstem response (ABR). In animal models, synaptopathy is associated with a reduction in ABR wave I amplitude at suprathreshold stimulus levels. Several human studies have explored the relationship between wave I amplitude and tinnitus, with conflicting results. This study investigates the hypothesis that reduced peripheral auditory input due to synaptic/neuronal loss is associated with tinnitus. ABR wave I amplitude data from 193 individuals (43 with tinnitus (22%), 150 without tinnitus (78%)), who participated in up to three out of four different studies, were included in a logistic regression analysis to estimate the relationship between wave I amplitude and tinnitus at a variety of stimulus levels and frequencies. Statistical adjustment for sex and distortion product otoacoustic emissions was included in the analysis. The results suggest that smaller ABR wave I amplitudes are associated with an increased probability of reporting tinnitus.


2021 ◽  
pp. 1-13
Author(s):  
Selis Gulseven Guven ◽  
Onur Ersoy ◽  
Ruhan Deniz Topuz ◽  
Erdoğan Bulut ◽  
Gulnur Kizilay ◽  
...  

<b><i>Introduction:</i></b> The effect of orally consumed monosodium glutamate (MSG), which is a common additive in the food industry, on the cochlea has not been investigated. The present study aimed to investigate the possible cochleotoxic effects of oral MSG in guinea pigs using electrophysiological, biochemical, and histopathological methods. <b><i>Methods:</i></b> Thirty guinea pigs were equally divided into control and intervention groups (MSG 100 mg/kg/day; MSG 300 mg/kg/day). At 1 month, 5 guinea pigs from each group were sacrificed; the rest were observed for another month. Electrophysiological measurements (distortion product otoacoustic emission [DPOAE] and auditory brainstem response [ABR]), glutamate levels in the perilymph and blood samples, and histopathological examinations were evaluated at 1 and 2 months. <b><i>Results:</i></b> Change in signal-to-noise ratio at 2 months was significantly different in the MSG 300 group at 0.75 kHz and 2 kHz (<i>p</i> = 0.013 and <i>p</i> = 0.044, respectively). There was no statistically significant difference in ABR wave latencies of the guinea pigs given MSG compared to the control group after 1 and 2 months; an increase was noted in ABR thresholds, although the difference was not statistically significant. In the MSG groups, moderate-to-severe degeneration and cell loss in outer hair cells, support cells, and spiral ganglia, lateral surface junction irregularities, adhesions in stereocilia, and partial loss of outer hair cell stereocilia were noted. <b><i>Conclusion:</i></b> MSG, administered in guinea pigs at a commonly utilized quantity and route of administration in humans, may be cochleotoxic.


2015 ◽  
Vol 129 (1) ◽  
pp. 38-45 ◽  
Author(s):  
F Aksoy ◽  
R Dogan ◽  
A Yenigun ◽  
B Veyseller ◽  
O Ozturan ◽  
...  

AbstractObjective:To investigate whether thymoquinone has any eliminative effects against inner-ear damage caused by acoustic trauma.Methods:Thirty-two male rats were divided into four groups. Group 1 was only exposed to acoustic trauma. Group 2 was given thymoquinone 24 hours before acoustic trauma and continued to receive it for 10 days after the trauma. Group 3 was only treated with thymoquinone, for 10 days. Group 4, the control group, suffered no trauma and received saline instead of thymoquinone. Groups 1 and 2 were exposed to acoustic trauma using 105 dB SPL white noise for 4 hours.Results:There was a significant decrease in distortion product otoacoustic emission values and an increase in auditory brainstem response thresholds in group 1 on days 1, 5 and 10, compared with baseline measurements. In group 2, a decrease in distortion product otoacoustic emission values and an increase in auditory brainstem response threshold were observed on day 1 after acoustic trauma, but measurements were comparable to baseline values on days 5 and 10. In group 3, thymoquinone had no detrimental effects on hearing. Similarly, the control group showed stable results.Conclusion:Thymoquinone was demonstrated to be a reparative rather than preventive treatment that could be used to relieve acoustic trauma.


2006 ◽  
Vol 120 (7) ◽  
pp. 524-527 ◽  
Author(s):  
Y Masuda ◽  
T Tanabe ◽  
Y Murata ◽  
S Kitahara

Objective: The purpose of this study was to determine the protective effect of edaravone, a free radical scavenger, on inner-ear barotrauma (IEB) in guinea pigs, based on a hypothesis implicating free radicals in the development of IEB.Materials and methods: One hundred and twenty-five guinea pigs were divided into a control group and a pretreatment group. After auditory brainstem response (ABR) testing, the pretreatment group received 9.0 mg/kg intraperitoneal edaravone. Animals were exposed to pressure loading and then to further ABR testing.Results: The incidence of IEB was 62.7 per cent in the control group and 42.9 per cent in the pretreatment group (p < 0.01). The distributions of threshold elevation in the control group were 37.3 per cent (for 10 dB or less), 21.3 per cent (for 20–30 dB), 18.0 per cent (for 40–60 dB) and 23.4 per cent (for 70 dB or more), and those in the pretreatment group were 57.1 per cent, 19.1 per cent, 14.3 per cent and 9.5 per cent, for the same respective decibel levels (p < 0.01).Conclusions: These results suggest that protective treatment with edaravone can significantly reduce both the incidence of IEB and the severity of the resultant ABR threshold elevation.


Author(s):  
Ö Gedik ◽  
H Hüsam ◽  
M Başöz ◽  
N Tas ◽  
F Aksoy

Abstract Objective This study aimed to evaluate different auditory regions with audiological tests, based on the presumption that there may be damage to the structures in the hearing system after coronavirus disease 2019. Methods Twenty individuals with no history of coronavirus disease 2019 and 27 individuals diagnosed with coronavirus disease 2019 were compared. Pure tone, speech and extended high-frequency audiometry, acoustic immitansmetry, transient evoked and distortion product otoacoustic emissions testing, and auditory brainstem response testing were conducted. Results The pure tone audiometry and extended high-frequency mean threshold values were higher in the coronavirus disease 2019 group. The transient evoked otoacoustic emissions signal-to-noise ratios were bilaterally lower at 4 kHz in individuals with a coronavirus disease 2019 history. In the auditory brainstem response test, only the interpeak latencies of waves III–V were significantly different between groups. Conclusion Coronavirus disease 2019 may cause damage to the hearing system. Patients should be followed up in the long term with advanced audiological evaluation methods in order to determine the extent and level of damage.


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