Protective effect of edaravone in inner-ear barotrauma in guinea pigs

2006 ◽  
Vol 120 (7) ◽  
pp. 524-527 ◽  
Author(s):  
Y Masuda ◽  
T Tanabe ◽  
Y Murata ◽  
S Kitahara
Keyword(s):  
Protective Effect ◽  
Inner Ear ◽  
Guinea Pigs ◽  
Auditory Brainstem ◽  
Free Radical Scavenger ◽  
Control Group ◽  
Radical Scavenger ◽  
Threshold Elevation ◽  
Brainstem Response ◽  
Inner Ear Barotrauma

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.

Antioxidant Enzyme Levels Inversely Covary with Hearing Loss After Amikacin Treatment

2003 ◽  
Vol 14 (03) ◽  
pp. 134-143 ◽  
Author(s):  
James J. Klemens ◽  
Robert P. Meech ◽  
Larry F. Hughes ◽  
Satu Somani ◽  
Kathleen C.M. Campbell
Keyword(s):  
Hearing Loss ◽  
Enzyme Activity ◽  
Antioxidant Enzyme ◽  
Guinea Pigs ◽  
Auditory Brainstem ◽  
Antioxidant Enzyme Activity ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Brainstem Response ◽  
The Difference

This study's purpose was to determine if a correlation exists between cochlear antioxidant activity changes and auditory function after induction of aminoglycoside (AG) ototoxicity. Two groups of five 250-350 g albino guinea pigs served as subjects. For 28 days, albino guinea pigs were administered either 200 mg/kg/day amikacin, or saline subcutaneously. Auditory brainstem response testing was performed prior to the first injection and again before sacrifice, 28 days later. Cochleae were harvested and superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase activities and malondialdehyde levels were measured. All antioxidant enzymes had significantly lower activity in the amikacin group (p ≤ 0.05) than in the control group. The difference in cochlear antioxidant enzyme activity between groups inversely correlated significantly with the change in ABR thresholds. The greatest correlation was for the high frequencies, which are most affected by aminoglycosides. This study demonstrates that antioxidant enzyme activity and amikacin-induced hearing loss significantly covary.

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 ◽  
...  
Keyword(s):  
Treatment Group ◽  
Protective Effect ◽  
Otoacoustic Emissions ◽  
Caspase 3 ◽  
Auditory Brainstem ◽  
New Drugs ◽  
Signal Frequency ◽  
Control Group ◽  
Distortion Product ◽  
Brainstem Response

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

scholarly journals Sulforaphane attenuates cisplatin-induced hearing loss by inhibiting histone deacetylase expression

2021 ◽  
Vol 35 ◽  
pp. 205873842110340
Author(s):  
Jie Wang ◽  
Ke-yong Tian ◽  
Ying Fang ◽  
Hui-min Chang ◽  
Ya-nan Han ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Protective Effect ◽  
Histone Deacetylase ◽  
Outer Hair Cell ◽  
Auditory Brainstem ◽  
Control Group ◽  
Protective Mechanism ◽  
Organotypic Cultures ◽  
Brainstem Response

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.

scholarly journals The Effects of Riluzole on Cisplatin-induced Ototoxicity

2019 ◽  
Vol 23 (03) ◽  
pp. e267-e275 ◽  
Author(s):  
Selin Üstün Bezgin ◽  
Kadir Kemal Uygur ◽  
Çağıl Gökdoğan ◽  
Çiğdem Elmas ◽  
Güleser Göktaş
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Protective Effect ◽  
Guinea Pigs ◽  
Neuronal Cell ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Transmission Electron ◽  
Significant Difference ◽  
Brainstem Response

Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity. Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in guinea pigs. Methods Twenty-four guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of cisplatin were administered to all animals for 3 days intraperitoneally (i.p.) to induce ototoxicity. Half an hour prior to cisplatin, groups 1, 2 and 3 received 2 ml of saline i.p., 6 mg/kg of riluzole hydrochloride i.p., and 8 mg/kg of riluzole hydrochloride i.p., respectively, for 3 days. The auditory brainstem responses were repeated 24 hours after the last drug administration. The cochleae were analyzed by transmission electron microscopy (TEM). Results After drug administiration, for 8,000 Hz stimulus, group 1 had significantly higher threshold shifts when compared with groups 2 (p < 0.05) and 3 (p < 0.05), and there was no significant difference in threshold shifts between groups 2 and 3 (p > 0.05). Transmission electron microscopy findings demonstrated the protective effect of riluzole on the hair cells and the stria vascularis, especially in the group treated with 8 mg/kg of riluzole hydrochloride. Conclusion We can say that riluzole may have a protective effect on cisplatin- induced ototoxicity. However, additional studies are needed to confirm these results and the mechanisms of action of riluzole.

Does Oral Monosodium Glutamate Have a Cochleotoxic Effect? An Experimental Study

2021 ◽  
pp. 1-13
Author(s):  
Selis Gulseven Guven ◽  
Onur Ersoy ◽  
Ruhan Deniz Topuz ◽  
Erdoğan Bulut ◽  
Gulnur Kizilay ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Outer Hair Cell ◽  
Monosodium Glutamate ◽  
Auditory Brainstem ◽  
Outer Hair Cells ◽  
Control Group ◽  
Distortion Product Otoacoustic Emission ◽  
Distortion Product ◽  
Significant Difference ◽  
Brainstem Response

<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.

Mitochondria-Targeted Antioxidant Mitoquinone Reduces Cisplatin-Induced Ototoxicity in Guinea Pigs

2016 ◽  
Vol 156 (3) ◽  
pp. 543-548 ◽  
Author(s):  
Alan D. Tate ◽  
Patrick J. Antonelli ◽  
Kyle R. Hannabass ◽  
Carolyn O. Dirain
Keyword(s):  
Hearing Loss ◽  
Auditory Brainstem Response ◽  
Guinea Pigs ◽  
Outer Hair Cell ◽  
Auditory Brainstem ◽  
Response Threshold ◽  
Saline Control ◽  
Control Group ◽  
Cochlear Hair Cells ◽  
Brainstem Response

Objective To determine if mitoquinone (MitoQ) attenuates cisplatin-induced hearing loss in guinea pigs. Study Design Prospective and controlled animal study. Setting Academic, tertiary medical center. Subjects and Methods Guinea pigs were injected subcutaneously with either 5 mg/kg MitoQ (n = 9) or normal saline (control, n = 9) for 7 days and 1 hour before receiving a single dose of 10 mg/kg cisplatin. Auditory brainstem response thresholds were measured before MitoQ or saline administration and 3 to 4 days after cisplatin administration. Results Auditory brainstem response threshold shifts after cisplatin treatment were smaller by 28 to 47 dB in guinea pigs injected with MitoQ compared with those in the control group at all tested frequencies (4, 8, 16, and 24 kHz, P = .0002 to .04). Scanning electron microscopy of cochlear hair cells showed less outer hair cell loss and damage in the MitoQ group. Conclusion MitoQ reduced cisplatin-induced hearing loss in guinea pigs. MitoQ appears worthy of further investigation as a means of preventing cisplatin ototoxicity in humans.

Effect of irradiation on guinea pig ABR thresholds

1992 ◽  
Vol 107 (6_part_1) ◽  
pp. 763-768 ◽  
Author(s):  
J. Scott Greene ◽  
Neil A. Giddings ◽  
John T. Jacobson
Keyword(s):  
Guinea Pigs ◽  
Auditory Brainstem ◽  
Control Group ◽  
Hearing Thresholds ◽  
Number Of Patients ◽  
Brainstem Response ◽  
Radiation Induced ◽  
The Difference ◽  
The Right ◽  
Temporal Bones

A significant number of patients undergo Irradiation to the temporal bone for malignancies. Conflicting reports exist regarding the effects of irradiation on hearing thresholds. Although radiation-induced otitis media and osteoradionecrosis of the ossicles with resultant conductive hearing loss are well-documented, there is disagreement regarding the effect of irradiation on sensorineural hearing. Previous animal models, relying only on behavioral tests and reflex thresholds, have failed to reveal consistent threshold shifts after irradiation. However, with the advent of auditory brainstem response (ABR) testing, a reliable objective measurement of hearing in animals is available. Hearing thresholds were determined bilaterally by ABR testing in 21 albino guinea pigs. The left temporal bones of sixteen animals were then Irradiated with a total dose ranging from 5750 to 7000 cGy over 7 weeks. The right ears of these animals, plus both ears of five nonlrradlated guinea pigs, served as controls. Follow-up threshold ABRs were obtained immediately post-irradlation (RT), and at 6 and 12 months post-RT. Average thresholds in all groups increased over time: 60 dB in the control group; 53 dB in the control ears of the Irradiated animals; and 46 dB in the Irradiated ears. There were no statistically significant increases in ABR thresholds for Irradiated ears vs. control ears. At the 6-month followup, hearing was actually better in the Irradiated ears than the control ears and this difference between ears was significantly greater than the difference at baseline ( p < 0.026). Overall, there was no evidence that irradiation produces changes in ABR thresholds.

Glutathione Ester But Not Glutathione Protects Against Cisplatin-Induced Ototoxicity in a Rat Model

2003 ◽  
Vol 14 (03) ◽  
pp. 124-133 ◽  
Author(s):  
Kathleen C.M. Campbell ◽  
Deb L. Larsen ◽  
Robert P. Meech ◽  
Leonard P. Rybak ◽  
Larry F. Hughes
Keyword(s):  
Auditory Brainstem Response ◽  
Outer Hair Cell ◽  
Tone Burst ◽  
Auditory Brainstem ◽  
Control Group ◽  
Brainstem Response ◽  
Group A ◽  
Direct Administration ◽  
Response Thresholds ◽  
Para Determinar

Glutathione (GSH) provides an important antioxidant and detoxification pathway. We tested to determine if direct administration of GSH or GSH ester could reduce cisplatin- (CDDP) induced ototoxicity. We tested eight groups of five rats each: a control group, a group receiving 16 mg/kg ip CDDP infused over 30 minutes, and six groups receiving either GSH or GSH ester at 500, 1000, or 1500 mg/kg intraperitoneally 30 minutes prior to 16 mg/kg CDDP. Auditory brainstem response thresholds were measured for click and tone-burst stimuli at baseline and 3 days later. Outer hair cell (OHC) loss was measured for the apical, middle and basal turns. The 500 mg/kg GSH ester reduced hearing loss and OHC loss, but protection decreased as dosage increased, suggesting possible toxicity. GSH was not significantly protective. The best GSH ester protection was less than we have previously reported with D-methionine. El glutatión (GSH) brinda una importante vía antioxidante y de cetoxificación. Realizamos una prueba para determinar si la administración directa de GSH o del éster de GSH podía reducir la ototoxicidad inducida por cisplatino (CDDP). Hicimos una evaluación en ocho grupos de cinco ratas cada uno: un grupo control, un grupo que recibió CDDP intraperitoneal a 16 mg/kg en una ínfusión durante 30 minutos y seis grupos que recibieron intraperitonealmente GSH o el éster de GSH a 500, 1000 o 1500 mg/kg, 30 minutos antes del CDDP a 16 mg/kg. Se midieron umbrales de respuestas auditivas del tallo cerebral tanto para clicks como para bursts tonales, al inicio y 3 días después. La pérdida de células ciliadas externas (OHC) fue establecida a nivel de las vueltas apical, media y basal. La dosis de 500 mg/kg de éster de GSH redujo la hipoacusia y la pérdida de OHC, pero la protección disminuyó conforme la dosis se incrementó, sugiriendo una posible toxicidad. EL GSH no resultó significativamente protector. El mejor efecto protector del éster de GSH fue menor que el previamente reportado con D-Metionina.

scholarly journals Prevention of acquired sensorineural hearing loss in mice by in vivo Htra2 gene editing

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xi Gu ◽  
Daqi Wang ◽  
Zhijiao Xu ◽  
Jinghan Wang ◽  
Luo Guo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Protective Effect ◽  
Hair Cell ◽  
Sensorineural Hearing Loss ◽  
Auditory Brainstem Response ◽  
Gene Editing ◽  
Auditory Brainstem ◽  
Sensorineural Hearing ◽  
Brainstem Response

Abstract Background Aging, noise, infection, and ototoxic drugs are the major causes of human acquired sensorineural hearing loss, but treatment options are limited. CRISPR/Cas9 technology has tremendous potential to become a new therapeutic modality for acquired non-inherited sensorineural hearing loss. Here, we develop CRISPR/Cas9 strategies to prevent aminoglycoside-induced deafness, a common type of acquired non-inherited sensorineural hearing loss, via disrupting the Htra2 gene in the inner ear which is involved in apoptosis but has not been investigated in cochlear hair cell protection. Results The results indicate that adeno-associated virus (AAV)-mediated delivery of CRISPR/SpCas9 system ameliorates neomycin-induced apoptosis, promotes hair cell survival, and significantly improves hearing function in neomycin-treated mice. The protective effect of the AAV–CRISPR/Cas9 system in vivo is sustained up to 8 weeks after neomycin exposure. For more efficient delivery of the whole CRISPR/Cas9 system, we also explore the AAV–CRISPR/SaCas9 system to prevent neomycin-induced deafness. The in vivo editing efficiency of the SaCas9 system is 1.73% on average. We observed significant improvement in auditory brainstem response thresholds in the injected ears compared with the non-injected ears. At 4 weeks after neomycin exposure, the protective effect of the AAV–CRISPR/SaCas9 system is still obvious, with the improvement in auditory brainstem response threshold up to 50 dB at 8 kHz. Conclusions These findings demonstrate the safe and effective prevention of aminoglycoside-induced deafness via Htra2 gene editing and support further development of the CRISPR/Cas9 technology in the treatment of non-inherited hearing loss as well as other non-inherited diseases.

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