S228 – Direct Round Window Drug Application and Ototoxicity in Rats

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P151-P151
Author(s):  
Teresa Rivera ◽  
Fernando García Alcantara ◽  
Jon Alexander Sistiaga Suarez ◽  
Murillo-Cuesta Silvia ◽  
Vacas Elena ◽  
...  

Objectives 1) Manage to introduce ototoxic drugs, such as kanamycin and furosemide, directly on the round window in rats. 2) Use a purified gelatine sponge as a proper delivery vehicle. The purpose of the study is to assess the validity of this method to provoke local ototoxicity. Methods We carried out an experimental design with 3 groups of 6 male Wistar rats. The bulla and round window membrane were exposed using a ventral approach. In the first control group we only made a hole in the tympanic bulla. Second control group was treated with saline solution. The problem group was treated with 20 mg/kg of kanamycin and 5 mg/Kg of furosemide-soaked gelatine sponge directly upon the round window membrane. Cochlear function was assessed through tone burst auditory brainstem response (ABR) threshold (dB) and peak latency (ms) measurements. Anova with bonferroni correction was used (p level=0.05). Results All animals treated with kanamycin and furosemide exhibited significant increase in ABR threshold (x = 51.25 dB; SD = 6.29; p = 0,001) in contrast to the other groups, whose ABR thresholds did not show significant differences before and after treatment(x=31,50 dB; SD=5.53); and not significant increase in peak latencies I (x = 0.22 ms; SD = 0.12), II (x = 0.22 ms; SD = 0.20) and IV (x = 0.21 ms; SD = 0.18). Conclusions The ventral approach and placement of kanamycin and furosemide-soaked gelatine sponge directly upon the round window membrane represents a reliable method for ototoxicity in rats.

2009 ◽  
Vol 141 (5) ◽  
pp. 584-590 ◽  
Author(s):  
Silvia Murillo-Cuesta ◽  
Fernando García-Alcántara ◽  
Elena Vacas ◽  
Jon Alexander Sistiaga ◽  
Guadalupe Camarero ◽  
...  

Objective: To assess the validity of inducing ototoxicity in rats by applying a sponge soaked in kanamycin and furosemide on the round window. Study Design: Basic, randomized, nonblind experimental study. Setting: Animal models of cochlear damage and reliable methods of local drug delivery are fundamental to study hearing loss and to design new therapies. Subjects and Methods: Four experimental groups of six Wistar rats with different methods of drug administration were used: (1) injection of subcutaneous kanamycin (400 mg/kg) and intravenous furosemide (100 mg/kg); (2) local application of a sponge soaked in saline close to the round window; (3) animals for which the sponge was soaked in a solution containing kanamycin (200 mg/mL) and furosemide (50 mg/mL); and (4) sham-operated rats. The tympanic bulla was exposed using a ventral approach, and a bullostomy was performed to visualize the round window membrane. Cochlear function was assessed by measuring the auditory brainstem response, and hearing thresholds in response to click and tone burst stimuli were determined as peak and interpeak latencies. At the end of the study, cochlear histology was analyzed. Results: Systemic administration of kanamycin and furosemide induced profound hearing loss and severe hair cell damage. Local delivery of these ototoxic drugs caused comparable damage but avoided the systemic side effects of the drug. Sham-operated and saline control animals did not experience functional alterations. Conclusion: Situating a sponge soaked in kanamycin and furosemide on the round window membrane through the ventral approach is a reliable method to provoke local ototoxicity in rats.


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

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.


2017 ◽  
Vol 131 (3) ◽  
pp. 245-252
Author(s):  
H Gur ◽  
Y Alimoglu ◽  
U Duzenli ◽  
S Korkmaz ◽  
S Inan ◽  
...  

AbstractBackground:Electrode insertion during cochlear implantation causes cochlear damage and apoptosis. Insulin-like growth factor applied locally was investigated in 21 rats.Methods:In the sham group, an intracochlear dummy electrode was inserted through the round window. In the control group, after the same insertion procedure, saline-soaked porcine skin gelatine was placed on the round window. In the study group, insulin-like growth factor 1 soaked gelatine was placed on the round window. Auditory brainstem response thresholds were measured and histopathological examination was performed.Results:In the study group, at 2–4 kHz, one rat had deterioration, one showed improvement and the rest had stable thresholds 14 days after intervention. At 6 kHz, four rats showed improvement and the rest remained stable. At 8 kHz, four showed improvement, one had deterioration and two remained stable. In the other groups, hearing loss deteriorated in about half of the rats and remained stable in the rest. The mean post-operative 6 kHz threshold was significantly lower than that immediately after the intervention in the study group, contrary to the other groups. The study group had significantly better mean histopathological grading than the other groups.Conclusion:Local insulin-like growth factor 1 application may protect hearing after cochlear implantation.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Xiang Liu ◽  
Xiao-qing Qian ◽  
Rui Ma ◽  
Fang-Lu Chi ◽  
Dong-Dong Ren

Different types of lasers have been used in inner ear surgery. Therefore, it is of the utmost importance to avoid damage to the inner ear (e.g., hyperthermia and acoustic effects) caused by the use of such lasers. The aim of this study was to use a high powered fibre-enabled CO2 laser (10 W, 606 J/cm2) to perform cochleostomies on guinea pig cochlea and to investigate the possible laser-induced damage mechanisms. The temperature changes in the round window membrane, auditory evoked brainstem response, and morphological of the hair cells were measured and recorded before and after laser application. All of the outcomes differed in comparison with the control group. A rise in temperature and subsequent increased hearing loss were observed in animals that underwent surgery with a 10 W CO2 laser. These findings correlated with increased injury to the cochlear ultrastructure and a higher positive expression of E-cadherin and β-catenin in the damaged organ of Corti. We assume that enhanced cell-cell adhesion and the activated β-catenin-related canonical Wnt-signalling pathway may play a role in the protection of the cochlea to prevent further damage.


2021 ◽  
Vol 11 (1) ◽  
pp. 38-46
Author(s):  
Fan-Yin Cheng ◽  
Craig A. Champlin

Temporal acuity is the ability to differentiate between sounds based on fluctuations in the waveform envelope. The proximity of successive sounds and background noise diminishes the ability to track rapid changes between consecutive sounds. We determined whether a physiological correlate of temporal acuity is also affected by these factors. We recorded the auditory brainstem response (ABR) from human listeners using a harmonic complex (S1) followed by a brief tone burst (S2) with the latter serving as the evoking signal. The duration and depth of the silent gap between S1 and S2 were manipulated, and the peak latency and amplitude of wave V were measured. The latency of the responses decreased significantly as the duration or depth of the gap increased. The amplitude of the responses was not affected by the duration or depth of the gap. These findings suggest that changing the physical parameters of the gap affects the auditory system’s ability to encode successive sounds.


2003 ◽  
Vol 14 (03) ◽  
pp. 134-143 ◽  
Author(s):  
James J. Klemens ◽  
Robert P. Meech ◽  
Larry F. Hughes ◽  
Satu Somani ◽  
Kathleen C.M. Campbell

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.


2020 ◽  
Vol 1 (1) ◽  
pp. 25-30
Author(s):  
Melita Hidajat ◽  
I Gusti Made Aman ◽  
Hendro Sukoco ◽  
Ferbian Milas Siswanto

The purpose of this study was to prove that the administration of Jati (Guazuma ulmifolia Lamk) leaves extract improves the lipid profile of dyslipidemic male Wistar rats. Subjects were 20 rats (Rattus norvegicus), male, Wistar strain, dyslipidemia (total cholesterol ≥ 200 mg dl-1), aged 2 months old, weighing 180-200 grams. The control group (10 rats) were given a placebo of 3 ml aquadest (P0) and the treatment group was given extracts of the Jati (Guazuma ulmifolia Lamk) leaves extract of 25 mg kg-1 BW (P1). Before and after treatment for 14 days, total cholesterol, triglyceride, LDL, and HDL levels were examined. The results showed that in the P0 group there were no changes in total cholesterol, triglyceride, LDL, and HDL levels (p>0.05), whereas the P1 group experienced a decrease in total cholesterol, triglyceride and LDL levels (p<0.05) and an increase in HDL levels (p<0.05). The results of this study indicated that the Jati leaves extract was effective to improve the lipid profile of dyslipidemic rats. It was necessary to compare the effectiveness of Jati leaves extract with synthetic dyslipidemia drugs used in the community such as statin.


Sign in / Sign up

Export Citation Format

Share Document